Refine
Has Fulltext
- yes (400)
Is part of the Bibliography
- yes (400)
Year of publication
Document Type
- Doctoral Thesis (289)
- Journal article (109)
- Conference Proceeding (1)
- Review (1)
Keywords
- HPLC (15)
- Pharmakokinetik (14)
- Aminosäuren (11)
- Fließverhalten (11)
- Arzneimittel (10)
- Arzneimitteldesign (10)
- Muscarinrezeptor (10)
- Bioverfügbarkeit (9)
- Inhibitor (9)
- Instrumentelle Analytik (9)
- NMR-Spektroskopie (9)
- Schüttgut (9)
- Flavonoide (8)
- Kapillarelektrophorese (8)
- Löslichkeit (8)
- Nanostrukturiertes Material (8)
- Biomarker (7)
- Chemische Synthese (7)
- Ligand <Biochemie> (7)
- Organische Synthese (7)
- Pharmakodynamik (7)
- Proteaseinhibitor (7)
- Qualitätskontrolle (7)
- Synthese (7)
- Tuberkelbakterium (7)
- Verunreinigung (7)
- metabolism (7)
- Arzneimittelforschung (6)
- Cytotoxizität (6)
- LC-MS (6)
- Legionella pneumophila (6)
- Massenspektrometrie (6)
- Metabolismus (6)
- Molekulardynamik (6)
- Proteinbindung (6)
- capillary electrophoresis (6)
- flavonoids (6)
- pharmacokinetics (6)
- polyphenols (6)
- synthesis (6)
- Analoga (5)
- Anthocyane (5)
- Candida albicans (5)
- Chromatographie (5)
- Computational chemistry (5)
- Cyclodextrine (5)
- Cysteinproteasen (5)
- Fließregulierung (5)
- Impurity Profiling (5)
- LC-MS/MS (5)
- Malaria (5)
- Permeabilität (5)
- Piperidinderivate (5)
- Polymere (5)
- Polyphenole (5)
- Pulver (5)
- Reinheitsanalytik (5)
- SARS (5)
- Stereoselektive Synthese (5)
- Stoffwechsel (5)
- Struktur-Aktivitäts-Beziehung (5)
- Synthesis (5)
- Trypanosomiase (5)
- Validierung (5)
- Wirkstoff (5)
- population pharmacokinetics (5)
- Antibiotikum (4)
- Aroma (4)
- Aziridine (4)
- Biotransformation (4)
- Charged Aerosol Detection (4)
- Chemische Reinheit (4)
- Chemometrie (4)
- Cyclodextrin (4)
- Enzyminhibitor (4)
- Extrakt (4)
- Extrazelluläre Matrix (4)
- Fließregulierungsmittel (4)
- GC-MS (4)
- GPCR (4)
- Hitzeschock-Proteine (4)
- Ionic Liquids (4)
- Kontrollierte Wirkstofffreisetzung (4)
- Lunge (4)
- Maisstärke (4)
- Molekulardesign (4)
- Pharmakotherapie (4)
- Protonen-NMR-Spektroskopie (4)
- Stabilität (4)
- Tandem-Reaktion (4)
- Targeted drug delivery (4)
- Trypanosomen (4)
- Wittig-Reaktion (4)
- allosteric modulation (4)
- antibiotics (4)
- chiral separation (4)
- cyclodextrin (4)
- drug design (4)
- molecular dynamics (4)
- muscarinic receptors (4)
- protein binding (4)
- therapeutic drug monitoring (4)
- validation (4)
- virtual screening (4)
- Acetylcholinesterase (3)
- Agonist (3)
- Amino acids (3)
- Aromastoff (3)
- Arzneimittelüberwachung (3)
- Auslauftrichter (3)
- Biosynthese (3)
- Burkholderia pseudomallei (3)
- Cholinesteraseinhibitor (3)
- Coronaviren (3)
- Diabetes mellitus (3)
- Docking (3)
- Elektronensprayionisations-Massenspektrometrie (3)
- Enantioselektivität (3)
- Ephedrin (3)
- Estradiol (3)
- Fließfähigkeit (3)
- Formulierungsentwicklung (3)
- Genexpression (3)
- Glucocorticoide (3)
- Glucocorticosteroide (3)
- HIV (3)
- HPLC-MS (3)
- Heilpflanzen (3)
- Inhibition (3)
- Insulin-like Growth Factor I (3)
- Interleukin 4 (3)
- KasA (3)
- Kiefernrindenextrakt (3)
- Knockout <Molekulargenetik> (3)
- Lungenperfusionsmodell (3)
- Maus (3)
- Multiples Myelom (3)
- Naturstoff (3)
- Pharmaceutical Analysis (3)
- Pharmazeutischer Hilfsstoff (3)
- Piperidinalkaloide (3)
- Plasmozytom (3)
- Procyanidine (3)
- Pycnogenol (3)
- Quantitative Analyse (3)
- Screening (3)
- Siliciumdioxid (3)
- Solubilisation (3)
- Strandkiefer (3)
- Strukturbasiertes Wirkstoffdesign (3)
- Ultrafiltration (3)
- Wasserlöslichkeit (3)
- Wirkstofffreisetzung (3)
- Zugspannung (3)
- amino acids (3)
- biomarker (3)
- charged aerosol detector (3)
- chemistry (3)
- click chemistry (3)
- drug delivery (3)
- flow regulation (3)
- flow regulator (3)
- flowability (3)
- human (3)
- mass spectrometry (3)
- medicine (3)
- natural products (3)
- neuroprotection (3)
- nutrition (3)
- oral bioavailability (3)
- pharmacodynamics (3)
- pharmacokinetic (3)
- plant extract (3)
- positron emission tomography (3)
- protease inhibitors (3)
- solubility (3)
- stereoselective synthesis (3)
- ultrafiltration (3)
- virtuelles Screening (3)
- AMSOL (2)
- ARONJ (2)
- Allosterischer Effektor (2)
- Alzheimer-Krankheit (2)
- Alzheimerkrankheit (2)
- Alzheimer’s disease (2)
- Aminosäure (2)
- Antibiotika (2)
- Antimikrobieller Wirkstoff (2)
- Aspartatproteasen (2)
- Asthma (2)
- Authentizität (2)
- Bioassay (2)
- Biologische Aktivität (2)
- Bitopische Liganden (2)
- Blutspiegel (2)
- Burkholderia (2)
- Butyrylcholinesterase (2)
- Capillary Electrophoresis (2)
- Carbamate (2)
- Chemie (2)
- Cholinesterase (2)
- Cyclo-GMP (2)
- Cytochrom P-450 (2)
- Cytokine (2)
- Derivatisierung (2)
- Diagnostik (2)
- Diffusion (2)
- Dimere (2)
- Dipolare Cycloaddition (2)
- Drug design (2)
- Enantiomere (2)
- Enantiomerentrennung (2)
- Enoyl-ACP-Reduktase (2)
- Enoyl-acyl-carrier-protein-Reductase (2)
- Enoyl-acyl-carrier-protein-Reductase <Enoyl-[acyl-carrier-protein]-Reductase> (2)
- Enterobacteriaceae (2)
- Entzündung (2)
- Erdbeere (2)
- Ernährung (2)
- Etacrynsäure (2)
- Europäisches Arzneibuch (2)
- FabI (2)
- Fettsäurebiosynthese (2)
- Fettsäuren (2)
- Fibroblastenwachstumsfaktor (2)
- Flavonoids (2)
- Fließeigenschaften (2)
- Fluoreszenz (2)
- Fluoreszenz-Resonanz-Energie-Transfer (2)
- Formulation development (2)
- Formulierung (2)
- Furaneol (2)
- GTP-bindende Proteine (2)
- Gentamicin (2)
- Glutathion (2)
- Granulieren (2)
- Gyrasehemmer (2)
- Heidelbeere (2)
- Hepatotoxizität (2)
- Hispidulin (2)
- Hitzeschocktranskriptionsfaktor (2)
- Humanstoffwechsel (2)
- Imatinib (2)
- In vitro (2)
- InhA (2)
- Isotopenverhältnis-Massenspektrometrie (2)
- Kräuterbücher (2)
- Lebensmittelchemie (2)
- Lebertoxizität (2)
- Legionärskrankheit (2)
- Leishmania (2)
- Lipide (2)
- Lipoxygenase <5-> (2)
- Marcophage-infectivity-potentiator-Protein (2)
- Maschinelles Lernen (2)
- Medizin (2)
- Melatonin (2)
- Membran (2)
- Merkaptursäuren (2)
- Metabolit (2)
- Metabolom (2)
- Mikroemulsion (2)
- Mittelalter (2)
- Molekülbibliothek (2)
- Multiple Myeloma (2)
- Muskarinrezeptor (2)
- Mutagenität (2)
- NMR spectroscopy (2)
- NMR-spectroscopy (2)
- Nanopartikel (2)
- Neuroprotektion (2)
- Osteoarthritis (2)
- Paracetamol (2)
- Permeation (2)
- Pharmacokinetic (2)
- Pharmacokinetics (2)
- Pharmakologie (2)
- Pharmazeutische Technologie (2)
- Pharmazie (2)
- Plasmodium falciparum (2)
- Polydimethylsiloxane (2)
- Polyethylenglykole (2)
- Polysiloxan-Membranen (2)
- Polysiloxane-Membranes (2)
- Poorly water soluble drugs (2)
- Populationskinetik (2)
- Populationspharmakokinetik (2)
- Positronen-Emissions-Tomografie (2)
- Proliferation (2)
- Protease (2)
- Protease-sensitive release (2)
- Protein-Protein-Wechselwirkung (2)
- Proteine (2)
- Pseudodistomin E (2)
- Pseudodistomine (2)
- QSAR (2)
- Random Chemistry (2)
- Regulation (2)
- Rezeptor (2)
- Rinde (2)
- S-ADAPT (2)
- STEC (2)
- Schlafkrankheit (2)
- Schüttgüter (2)
- Selektivität (2)
- Serumalbumine (2)
- Signaltransduktion (2)
- Spiralstrahlmühle (2)
- Stability (2)
- Staphylococcus aureus (2)
- Statistische Thermodynamik (2)
- Stickstoffmonoxid (2)
- Structure-based drug design (2)
- Supersaturation (2)
- T cells (2)
- T-Zellen (2)
- Tandem Wittig-[3+2]-Cycloaddition (2)
- Tandem-Massenspektrometrie (2)
- Therapeutic Systems (2)
- Therapeutische Systeme (2)
- Therapeutisches Drug Monitoring (2)
- Thermodynamik (2)
- Tissue Engineering (2)
- Totalsynthese (2)
- Tryptophan (2)
- Tuberkulose (2)
- Valeriana wallichii (2)
- Verkapselung (2)
- Verunreinigungsprofil (2)
- Virtuelles Screening (2)
- Wirbelschichtgranulation (2)
- Wirbelschichtverfahren (2)
- Wirkstoffdesign (2)
- Würzburg / Institut für Geschichte der Medizin / Forschungsgruppe Klostermedizin (2)
- Zellkultur (2)
- albumin (2)
- allometric scaling (2)
- amino acid (2)
- anthocyanins (2)
- antibiotic (2)
- antileishmanial (2)
- apple juice (2)
- authenticity (2)
- aziridines (2)
- azobenzenes (2)
- baclofen (2)
- body composition (2)
- body size (2)
- bulk powders (2)
- butyrylcholinesterase (2)
- chirale Trennung (2)
- clinical study (2)
- corn starch (2)
- coronavirus (2)
- crystal structure (2)
- cyclodextrins (2)
- cysteine protease (2)
- cystic fibrosis patients (2)
- cytochrome P450 3A4 (CYP3A4) (2)
- cytotoxicity (2)
- dendritic cells (2)
- docking (2)
- drugs (2)
- drug–drug interactions (DDIs) (2)
- dualsteric ligands (2)
- endothelium (2)
- estrogens (2)
- etacrynic acid (2)
- extracellular matrix (2)
- fatty acid biosynthesis (2)
- fatty acids (2)
- flavor (2)
- flavour (2)
- gene expression (2)
- glidants (2)
- glutathione (2)
- graft versus host disease (2)
- healthy volunteers (2)
- herbal medicines (2)
- hispidulin (2)
- human breast (2)
- impurities (2)
- impurity profiling (2)
- in vitro (2)
- inflammation (2)
- inhibitors (2)
- ion-pair chromatography (2)
- isotope ratio mass spectrometry (2)
- kinetics (2)
- leishmaniasis (2)
- liquid chromatography (2)
- malaria (2)
- marine sponge (2)
- matrix metalloproteinase (2)
- mercapturic acids (2)
- metabolomics (2)
- molecular modeling (2)
- molekulardynamische Simulationen (2)
- multiple linear regression (2)
- muscarinic receptor (2)
- nitric oxide (2)
- norepinephrine transporter (2)
- octopamine (2)
- organic synthesis (2)
- osteoarthritis (2)
- osteonecrosis of the jaw (2)
- osteoradionecrosis (2)
- outflow funnel (2)
- permeability (2)
- pharmaceutical analysis (2)
- physiologically based pharmacokinetic (PBPK) modeling (2)
- pine bark extract (2)
- piperidine derivatives (2)
- precipitated silica (2)
- protease (2)
- protease inhibitor (2)
- pseudodistomine E (2)
- qNMR (2)
- random chemistry (2)
- regulation (2)
- screening (2)
- spiral jet mill (2)
- staphylococcus aureus (2)
- stereoselektive Synthese (2)
- strategy (2)
- structure-activity relationship (2)
- structure-activity relationships (2)
- sympathetic nervous system (2)
- tandem Wittig-[3+2]-cycloaddition reaction (2)
- therapy (2)
- thermogenesis (2)
- trypanosomiasis (2)
- Öl (2)
- "Random Chemistry" (1)
- (+)-Catechin (1)
- - (1)
- 1 (1)
- 17beta-Estradiol (1)
- 17beta-estradiol (1)
- 2 (1)
- 2,5-diketopiperazines (1)
- 2-(Phenylsulfonylmethyl)-piperidin (1)
- 2-(Phenylsulfonylmethyl)-piperidine (1)
- 2-Thiazaphospholidines (1)
- 2-a:6 (1)
- 2-chloro (1)
- 2-halo (1)
- 2-imino- (1)
- 3 (1)
- 3-(R)-Hydroxysäuren (1)
- 3-(R)-hydroxy acids (1)
- 3-dipolar cycloaddition (1)
- 3-dipolare Cycloaddition (1)
- 4-Chinolonamid (1)
- 4-dial (1)
- 4-quinolone (1)
- 4-quinolone-derivatives (1)
- 4D-QSAR (1)
- 5-Aminopiperidylessigsäuren (1)
- 5-Dimethyl-4-hydroxy-3(2H)-furanon (1)
- 5-Dimethyl-4-hydroxy-3(2H)-furanone (1)
- 5-Dimethyl-4-methoxy-3(2H)-furanon (1)
- 5-Dimethyl-4-methoxy-3(2H)-furanone (1)
- 5-a']diindol (1)
- 5-a']diindole (1)
- 5-aminopiperidylaceticacid (1)
- 5-b']diindol (1)
- 5-b']diindole (1)
- 5]diazocino[1 (1)
- 77-LH-28-1 (1)
- 8-Oxo-2’-desoxyguanosin (1)
- 8-oxo-2'-deoxyguanosine (1)
- AAA+ ATPase p97 (1)
- ABC-Transporter (1)
- AChE inhibitor (1)
- AD mouse modele (1)
- ADAM-10 (1)
- ADAMTS (1)
- AFM (1)
- AGP (1)
- AL amyloidosis (1)
- AL-Amyloidose (1)
- AOM/DSS (1)
- Acetaminophen (1)
- Acetylcysteinderivate (1)
- Achillea Fragrantissima (1)
- Acrylamid (1)
- Acrylamide (1)
- Actinomycetes (1)
- Active pharmaceutical ingredients (1)
- Acylierte Quercetin-Tri-Glukoside (1)
- Acyltransferasen (1)
- Addukt (1)
- Adenosin (1)
- Adhäsion (1)
- Aerosil (1)
- Aerosile (1)
- Aescin (1)
- Affinitätsindex (1)
- African Trypanosomiasis (1)
- Agomelatin (1)
- Ah Rezeptor (1)
- Ah receptor (1)
- Akt (1)
- Akt/PKB (1)
- Alanyl-Aminopeptidase (1)
- Albendazol (1)
- Albumin (1)
- Aldehyde (1)
- Aldehydreductase (1)
- Aldose Reductase (1)
- Aldose Reduktase (1)
- Aldosteron (1)
- Alkamiden (1)
- Alkamides (1)
- Alkylpyrazine (1)
- Allostere Modulation (1)
- Allosterer Modulator (1)
- Allosteric Modulator (1)
- Allosterisch Modurator (1)
- Alzheimer (1)
- Alzheimer's Disease (1)
- Alzheimer's diseas (1)
- Alzheimer's disease (1)
- Alzheimer′s disease (1)
- Ambulante Behandlung (1)
- Amino Acids (1)
- Aminoethanolderivate (1)
- Aminoglykoside (1)
- Ammoniumverbindungen (1)
- Amphetamin (1)
- Amyloid <beta-> (1)
- Amyloidose (1)
- Anacardic acid derivatives (1)
- Anacardsäurederivate (1)
- Analyse (1)
- Analytical Quality by Design (1)
- Analytik (1)
- Analytische Chemie (1)
- Anandamid (1)
- Angeborene Immunität (1)
- Angiogenese (1)
- Angiotensin II (1)
- Antagonist (1)
- Antibiotic (1)
- Antifungal (1)
- Antigen (1)
- Antigen CD163 (1)
- Antiinfektiva (1)
- Antiinflammatorisch (1)
- Antikörper (1)
- Antimykotika (1)
- Antioxidans (1)
- Antiphlogistikum (1)
- Antitrypanosomal (1)
- Antitrypanosomen (1)
- Antitumor (1)
- Antivira (1)
- Apfelsaft (1)
- Apobec (1)
- Arabischer Kaffee (1)
- Arbutin (1)
- Aromaprofil (1)
- Artemisia dracunculus (1)
- Arthrose (1)
- Arylamine (1)
- Arylgruppe (1)
- Arzneimittelfälschungen (1)
- Arzneimittelwechselwirkung (1)
- Arzneistoffanalytik (1)
- Arzneistoffe (1)
- Arzneistofftransporter (1)
- Aspartat-Proteasen (1)
- Aspergillosis (1)
- Aspergillus (1)
- Asymmetrie (1)
- Asymmetrische Synthese (1)
- Atropin (1)
- Auflösungsraten (1)
- Aufmerksamkeitsdefizit-Syndrom (1)
- Aurora-A (1)
- Aurora-A-MYCN-Komplex (1)
- Automatisierung (1)
- Autoradiographie (1)
- Außenluftfeuchte (1)
- Aza-Peptide (1)
- Aza-Peptides (1)
- Azapeptide (1)
- Aziridin (1)
- Aziridin-2-carboxylate (1)
- Aziridines (1)
- BRAF mutation (1)
- Bacillus megaterium (1)
- Baclofen (1)
- Bacteria (1)
- Bakterien (1)
- Beclomethason (1)
- Beclomethasondipropionat (1)
- Benzimidazole (1)
- Benzodiazepin-Rezeptor-Liganden (1)
- Benzodiazepine receptor ligands (1)
- Beta-2-Rezeptor (1)
- Betalaine (1)
- Betanin (1)
- Betanine (1)
- Bile (1)
- Bindemechanismus (1)
- Bindungsaffinität (1)
- Bindungskonstante (1)
- Bioaccessibility (1)
- Bioaktivität (1)
- Bioanalytik (1)
- Bioavailability (1)
- Bioconjugate (1)
- Biodistribution (1)
- Biofunctionality (1)
- Biofunktionalität (1)
- Biohydroxylierung (1)
- Biokatalyse (1)
- Biokonversion (1)
- Biologischer Abbau (1)
- Bioreactor System (1)
- Biosensor (1)
- Biostatistik (1)
- Biosynthesis (1)
- Bipyridinediylbisboranes / Redox systems / Cyclovoltammetry (1)
- Bis-Tacrine (1)
- Bisoprolol (1)
- Bisphosphonate (1)
- Bitopic Ligands (1)
- Bivalente Hybridverbindungen (1)
- Blaubeere (1)
- Blinddarm (1)
- Blockcopolymere (1)
- Blut (1)
- Blut-Hirn-Schranke (1)
- Bodenbakterien (1)
- Bronchialasthma (1)
- Brunschwig (1)
- Brust (1)
- Brustdrüse (1)
- Brückenbildung (1)
- Burkholderia pseudomallei Mip (1)
- C-3-substituiert (1)
- C-3-substituted (1)
- CAD detection (1)
- CAR T cells (1)
- CAR T-Zellen (1)
- CCl4-induzierte Leberfibrose (1)
- CD163 (1)
- CE (1)
- CFC replacements (1)
- CNS (1)
- COSMOtherm (1)
- CO‐releasing molecules (CORMs) (1)
- CYP2C9 (1)
- CYP3A4 (1)
- CZE (1)
- CaCo-II-Zellen (1)
- Cabozantinib (1)
- Calmodulin (1)
- Campylobacter jejuni (1)
- Candida auris (1)
- Cannabidiol (1)
- Cannabidivarin (1)
- Cannabinoid Receptor (1)
- Cannabinoide (1)
- Carbocistein (1)
- Carbolin <beta-> (1)
- Carboxylates (1)
- Cassins (1)
- Catechin C-glykoside (1)
- Catechin C-glykosides (1)
- Catechine (1)
- Catecholestrogene (1)
- Catecholmethyltransferase <Catechol-0-Methyltransferase> (1)
- Cathepsin (1)
- Cecropia telenitida (1)
- Cerulenin (1)
- Characterization (1)
- Charged Aerosol Detektion (1)
- Charged aerosol detection (1)
- Charged aerosol detector (CAD) (1)
- Chemical stability (1)
- Chemische Analyse (1)
- Chemometric (1)
- Chemometrics (1)
- Chewing Gum (1)
- Chinazoline (1)
- Chinazoliniumverbindungen (1)
- Chinazolinone (1)
- Chinolinderivate (1)
- Chinolon <2-> (1)
- Chinolonamide (1)
- Chinolonderivate (1)
- Chinolonderivate <2-> (1)
- Chinolone (1)
- Chinon-oxidoreduktase (1)
- Chirale Trennung (1)
- Chiralität (1)
- Chlorfluorkohlenstoffe (1)
- Chondrogenesis (1)
- Chondrozyten (1)
- Chromatographischer Detektor (1)
- Chromone (1)
- Cisaprid (1)
- Cisapride (1)
- Citrus (1)
- Click-Chemie (1)
- Clotrimazol (1)
- Codon (1)
- Coffea arabica (1)
- Coffein (1)
- Colon-Targeting (1)
- Commercial preparations (1)
- Computational drug-design (1)
- Confocal Raman-Spectroscopy (1)
- Contaminants (1)
- Controlled release (1)
- Corona charged aerosol detector (1)
- Coronavirus (1)
- Counterfeit Medicines (1)
- Cutaneous leishmaniasis (1)
- Cyclo-AMP (1)
- Cycload (1)
- Cycloaddition (1)
- Cyclooxygenase (1)
- Cyperus (1)
- Cystein (1)
- Cystein-Protease (1)
- Cystein-Proteasen (1)
- Cytochrom-P450-Enzym (1)
- Cytochrom-P450-Enzyme, Carboxylesterasen, Glutathion-S-Transferasen (1)
- Cytochromperoxidase (1)
- Cytotoxicity (1)
- Cytotoxiticity-Assay (1)
- DAF-2 (1)
- DNA base excision repair (1)
- DNA-Basen (1)
- DNA-Reparatur (1)
- DNA-encoded library synthesis (1)
- DNA-tagged amines (1)
- DNS-Chip (1)
- DPP IV (1)
- Daptomycin (1)
- Datenanalyse (1)
- Datenauswertung (1)
- Deep Eutectics (1)
- Demethylierung (1)
- Deoxyhypusinhydroxylase (1)
- Derivatization (1)
- Derivsatisierung (1)
- Destillierbücher (1)
- Detektor (1)
- Determination of compound purity (1)
- Diazabicyclononan (1)
- Diazabicyclononane (1)
- Diazabicyclononanone (1)
- Dicarbonyl (1)
- Dickdarm (1)
- Dickdarmkrebs (1)
- Differentielle Genexpression (1)
- Differenzierung (1)
- Diffusionskonstante (1)
- Dihydroisochinolinderivate (1)
- Dihydroisochinolinonderivate (1)
- Dihydroxynaphthaline (1)
- Dimere Tacrinverbindungen (1)
- Dimerisierung (1)
- Dioxine (1)
- Dioxygenasen (1)
- Dipeptide (1)
- Diphosphonate (1)
- Direkttablettierung (1)
- Diskriminanzanalyse (1)
- Dissertation (1)
- Docking <Chemie> (1)
- Docking protein (1)
- Dockingstudien (1)
- Dosis (1)
- Dosislinearität (1)
- Dreistoffgemisch (1)
- Dronabinol (1)
- Druck (1)
- Drug delivery platform (1)
- Drug delivery platforms (1)
- Drug form selection (1)
- Dünnschichtchromatographie (1)
- EA.hy 926 (1)
- EDC-NHS chemistry (1)
- EDTA (1)
- ESI-MS (1)
- East Africa (1)
- Echium spp. (1)
- Effluxpumpen (1)
- Einschlusskomplex (1)
- Einschlussverbindungen (1)
- Electron Density (1)
- Electrospinning (1)
- Elektronendichte (1)
- Elongin-C Protein-Protein Interaktion (1)
- Elongin-C protein-protein interaction (1)
- Enantiodifferenzierung (1)
- Enantiomerüberschuss (1)
- Enantioselectivity (1)
- Encapsulation (1)
- Endothel (1)
- Endothelzelle (1)
- Enoyl-Reduktase (1)
- Enoyl-acyl-carrier-protein-Reductase<Enoyl-[acyl-carrier-protein]-Reductase> (1)
- Enzym (1)
- Enzym Assays (1)
- Enzymatische Aktivität (1)
- Enzymatische Oxidation (1)
- Enzyme (1)
- Enzyme Assays (1)
- Enzyme inhibitor (1)
- Enzymkinetik (1)
- Epoxide (1)
- Erbse (1)
- Erdbeeren (1)
- Erdmandel (1)
- Eriodictyon californicum (1)
- Ersatzstoff (1)
- Eruca sativa Mill. (1)
- Erythromycin (1)
- Escherichia coli (1)
- EspI (1)
- Estradiolkonjugate (1)
- Estrogens (1)
- Ethambutol (1)
- European Pharmacopoeia (1)
- Europäsches Arzneibuch (1)
- Ex vivo (1)
- Ex-Chiral-Pool Synthese (1)
- Excipient selection (1)
- Excipients (1)
- Expiry date (1)
- Expositionsmarker (1)
- Expression (1)
- Exzitotoxizität (1)
- FCKW-Ersatzstoffe (1)
- FGF (1)
- FGF-2 (1)
- FKBP (1)
- FRET (1)
- FRET-Assay (1)
- FRET-assay (1)
- FSME (1)
- FV45 (1)
- FadA5 (1)
- Fatty acids (1)
- Feigenkaktus (1)
- Fentons Reagenz (1)
- Fermentation (1)
- Fertigarzneimittel (1)
- Fest-Flüssig-Extraktion (1)
- Festkörper-NMR (1)
- Festkörper-NMR-Spektroskopie (1)
- Festkörperoberfläche (1)
- Festphasenextraktion (1)
- Fett (1)
- Fettabbau (1)
- Fettgewebe (1)
- Fettkennzahlen (1)
- Fettsäureabbau (1)
- Fettsäuremetabolismus (1)
- Fettsäurestoffwechsel (1)
- Fettsäuresynthese-II (1)
- Feuchtemessung (1)
- Feuchtigkeitsmessung (1)
- Fibroblasten-Aktivierungs-Protein Alpha (1)
- Fl (1)
- FlAsH (1)
- Flammschutzmittel (1)
- Flavonglykoside (1)
- Flavoniden (1)
- Flavonoidstoffwechsel (1)
- Flavonoinds (1)
- Flavor (1)
- Fleisch (1)
- Fleischerzeugnisse (1)
- Flexibilität (1)
- Fluidized bed granulation process (1)
- Fluor-19-NMR-Spektroskopie (1)
- Fluorchinolone (1)
- Fluoreszenz <Motiv> (1)
- Fluoreszenzassay (1)
- Fluoreszenzliganden (1)
- Fluoreszenzmikroskopie (1)
- Fluoreszenzpolarisation (1)
- Fluorine (1)
- Fluorverbindungen (1)
- Flux (1)
- Flüssigkeitschromatographie (1)
- Foldamer (1)
- Foldamere (1)
- Foldamers (1)
- Formaldehyd (1)
- Formulation (1)
- Fraktale Dimension (1)
- Freeze drying (1)
- Freie Energierechnungen (1)
- Freisetzung (1)
- Fruchtreife (1)
- Fruchtsaft (1)
- Fumonisine (1)
- Fumonisins (1)
- Functional properties (1)
- Funktionalisierung <Chemie> (1)
- Funktionalisierung von elektrogesponnenen Fasern (1)
- Furan (1)
- Furanon (1)
- Furanone (1)
- Fälschung (1)
- G-Protein gekoppelte Rezeptor (1)
- G-Protein gekoppelte Rezeptoren (1)
- G-Proteine (1)
- G-protein coupled receptor (1)
- GABA (1)
- GABA-Rezeptor-Agonist (1)
- GABAB (1)
- GABAB receptor agonists (1)
- GABA\(_{A}\) receptor (1)
- GABA\(_{B}\) (1)
- GC-MS-SCD (1)
- GRK2 (1)
- Galle (1)
- Galle <Sekret> (1)
- Gallensalze (1)
- Gallensäuren (1)
- Gartenrauke (1)
- Gas chromatography (1)
- Gaschromatographie (1)
- Gastrointestinaltrakt (1)
- Gefriertrocknung (1)
- Gehaltsbestimmung (1)
- Genanalyse (1)
- Genotoxizität (1)
- Gentoxizität (1)
- Geschichte (1)
- Geschwindigkeit (1)
- Gesundheitsberatung (1)
- Gewebe (1)
- Gewebebindung (1)
- Gewebespende (1)
- Gewebespiegel (1)
- Gewinnung und Funktionale Analyse von Wirkstoffen gegen Infektionskrankheiten (1)
- Gewürz (1)
- Gewürzextrakte (1)
- Glatte Muskulatur (1)
- Glucocorticoids (1)
- Glutamate (1)
- Glutamatrezeptoren (1)
- Glycinrezeptor (1)
- Glycoengineering (1)
- Glykane <N-> (1)
- Glykoside (1)
- Glykosylierung (1)
- Gradient boosted trees (GBT) (1)
- Grüner Kaffee (1)
- Grünnoten (1)
- Guanfacin (1)
- Guanylatcyclase (1)
- Guillain-Barr'e-Syndrom (1)
- Guillain-Barré Syndrom (1)
- Guillain-Barré syndrome (1)
- Gärungsalkohole (1)
- HDMF (1)
- HIC (1)
- HILIC (1)
- HNSCC (1)
- HPLC method development (1)
- HPLC-MS/MS (1)
- HPLC-Methodenentwicklung (1)
- HPLC/UV, HPLC/fluorescence, LC/MS/MS analysis (1)
- HPLC/UV-, HPLC/Fluoreszenz-, LC/MS/MS-Analyse (1)
- HPLC–MS (1)
- HSF-1 (1)
- HSP70 (1)
- HUVEC (1)
- Harn (1)
- Hauptkomponentenanalyse (1)
- Hausner-Faktor (1)
- Haut Baleichung (1)
- Haut Bleichung (1)
- Heatshock Proteins (1)
- Hefeartige Pilze (1)
- Heparansulfat (1)
- Heparin (1)
- Hepatitis-B-Virus (1)
- Herkunft (1)
- Herkunftsnachweis (1)
- Herzschrittmacher (1)
- Hess theorem (1)
- Hess'scher Satz (1)
- Hieronymus (1)
- Hieronymus Brunschwig (1)
- High-performance liquid chromatography (1)
- High-performance liquid chromatography (HPLC) (1)
- Hildegard <von Bingen> (1)
- Hildegard von Bingen (1)
- Hilfsstoffanalytik (1)
- Hirnzelle (1)
- Hitzeschock Proteine (1)
- Hitzeschockproteine (1)
- Honig (1)
- Hsc70 (1)
- Hsp70 (1)
- Humane Afrikanische Trypanosomiasis (1)
- Humanserum (1)
- Hyaliner Gelenkknorpel (1)
- Hybrid (1)
- Hybrid GPCR Ligands (1)
- Hybrid-Molecules (1)
- Hybridliganden (1)
- Hydrogen-deuterium (1)
- Hydroperoxide (1)
- Hydrophobe Wechselwirkung (1)
- Hydroxycarbonsäuren (1)
- Hydroxylradikal (1)
- Hypoxanthin-Guanin-Phosphoribosyl-Transferase (1)
- Hypoxia (1)
- Hypoxie (1)
- Hülsenfrüchte (1)
- IGF-1 (1)
- IGF-I (1)
- IR (1)
- IRMS (1)
- ISPMF (1)
- Ibuprofen (1)
- Imidates (1)
- Imidoyl halides (1)
- Immunmodulation (1)
- Immunohistologie (1)
- Immunosuppressant (1)
- Immunreaktion (1)
- Immunsuppressiva (1)
- Impact-Faktor (1)
- Impurity Profile (1)
- In vivo (1)
- In vivo studies (1)
- In-vitro-Assays (1)
- Indolderivate (1)
- Infektionskrankheit (1)
- Infusionslösungen (1)
- Inhalation (1)
- Inhalationsmittel (1)
- Inhibitoren der Acetylcholinesterase (1)
- Inhibitorpeptide (1)
- Insulin-like Growth Factor (1)
- Insulin-like growth factor-I (1)
- Integrasen (1)
- Interferon <alpha-2a-> (1)
- Interleukin (1)
- Ion Pairs (1)
- Ionenchromatographie (1)
- Ionenkanal (1)
- Ionenpaarchromatographie (1)
- Ionentauscher (1)
- Ionexchange (1)
- Ionic Liquid (1)
- Ionische Flüssigkeit (1)
- Ionische Flüssigkeiten (1)
- Ipratropiumbromid (1)
- Isochinolinalkaloide (1)
- Isochinolinderivate (1)
- Isocyanate (1)
- Isoindoline (1)
- Isolation and Characterization (1)
- Isolierung <Chemie> (1)
- Isoprostaglandin (1)
- Isotopendiskriminierung (1)
- Isotopenhäufigkeit (1)
- Isotopenmarkierung (1)
- Isotopenmassenspektroskopie (1)
- Isotpe ratio mass spectrometry (1)
- JAK inhibitor (1)
- Jugend (1)
- Jugendliche (1)
- Kaktusfeige (1)
- Kaliumkanal (1)
- Kalorimetrie (1)
- Kaltgepresstes Öl (1)
- Kappa (1)
- Karibisches Meer (1)
- Kaugummi (1)
- Keimling (1)
- Keimung (1)
- Kernrezeptor (1)
- Kernspinrelaxation (1)
- Ketamin (1)
- Ketoacyl-ACP-Synthase <beta-> (1)
- Ketoacyl-ACP-Synthase <beta> (1)
- Ketoacyl-ACP-synthase (1)
- Ketosulfon (1)
- Kinaseinhibitor (1)
- Kind (1)
- Kinder (1)
- Klebsiella pneumoniae (1)
- Klinische Studie (1)
- Kniegelenk (1)
- Knochenpenetration (1)
- Knock out (1)
- Knock-out Maus (1)
- Knorpelbildung (1)
- Kohlenhydrate (1)
- Kohlenmonoxid (1)
- Kohlenstoff-14 (1)
- Kohlenwasserstoffe (1)
- Kohäsion (1)
- Kokristallisation (1)
- Konfokale Mikroskopie (1)
- Konfokale Raman-Spektroskopie (1)
- Konformationsanalyse (1)
- Konformationsänderung (1)
- Konjugate (1)
- Konjugation (1)
- Konzentrat (1)
- Kreatinin (1)
- Kristall (1)
- Kristallisation (1)
- Kristallstruktur (1)
- Kupffer-Sternzelle (1)
- LC-ESI/MS/MS (1)
- LMICS (1)
- LPA (1)
- Lactamantibiotikum <beta-> (1)
- Lactone (1)
- Lactose (1)
- Laserbeugungsanalyse (1)
- Lebensmittel (1)
- Lebensmittelanalyse (1)
- Lebensmittelprodukte (1)
- Leber (1)
- Leberfibrose (1)
- Legionella infection (1)
- Legionellen (1)
- Legionelleninfektion (1)
- Legionnaires' Disease (1)
- Legionnaires' disease (1)
- Leishmaniose (1)
- Leitstrukturoptimierung (1)
- Leonhart Fuchs (1)
- Levodopa (1)
- Library of Phytochemicals (1)
- Library of plant species (1)
- Ligand (1)
- Linezolid (1)
- Lipid-Peroxide (1)
- Liposomen (1)
- Lipoxygenase (1)
- Lokaltherapie (1)
- Low-income Countries (1)
- LpxC inhibitors (1)
- Luftfeuchtigkeit (1)
- Lungenentzündung (1)
- Lungengewebe (1)
- Lungenkrebs (1)
- Lungenperfusion (1)
- Lyophilisate zum Einnehmen (1)
- Löslichkeitsstudien (1)
- Löslichkeitsverbesserung (1)
- Lösungsprozess (1)
- M. tuberculosis (1)
- M1 Muscarinic Receptor (1)
- M2 (1)
- M4 (1)
- MALDI-MS (1)
- MD simulation (1)
- MD simulations (1)
- MD-Simulationen (1)
- MDR (1)
- MEEKC (1)
- MEKC (1)
- MIP protein (1)
- MIR-Spektroskopie (1)
- MRONJ (1)
- MRSA (1)
- MS (1)
- MTUS1 (1)
- MYCN (1)
- MYCNv (1)
- Macrogol (1)
- Macrogole (1)
- Macrophage Infectivity Potentiator Protein (1)
- Macrophage infectivity potentiator Protein (1)
- Magnetische Kernresonanz (1)
- Makroarray (1)
- Makrophage (1)
- Manganese Carbonyl ligands (1)
- Mannich-Reaktion (1)
- Manteltiere (1)
- Markierte Verbindungen (1)
- Masernvirus (1)
- Masernvirus Inhibitoren (1)
- Mass spectrometry (1)
- Massenbilanzierung (1)
- Masspectrometry (1)
- Matrix Effekte (1)
- Matrixmetalloproteinase (1)
- Mebendazol (1)
- Mehrkomponentengemische (1)
- Melatonin-Analoga (1)
- Melatoninrezeptorliganden (1)
- Messung (1)
- Metabolisches Syndrom (1)
- Metabolism (1)
- Metabolismusstudien (1)
- Metabolomics (1)
- Metabolomik (1)
- Metabonomics (1)
- Metalloproteinasen (1)
- Metformin (1)
- Method Validation (1)
- Methode der partiellen kleinsten Quadrate (1)
- Methodenentwicklung (1)
- Methylanthranilat (1)
- Methylation (1)
- Methylierung (1)
- Micellare elektrokinetische Kapillarchromatographie (1)
- Microarray (1)
- Microglia (1)
- Microwave Assisted Extraction (1)
- Midazolam (1)
- Mikroorganismen (1)
- Mikroorganismus (1)
- Mikroskopie (1)
- Mikrosphären (1)
- Milchdrüse (1)
- Mineralokortikoidrezeptor (1)
- Mip (1)
- Mip Inhibitoren (1)
- Mip inhibitor (1)
- Mip-Inhibitor (1)
- Mischintensität (1)
- Mitochondrium (1)
- Mitsunobu (1)
- Mizellen (1)
- Modellberechnungen (1)
- Modellbindetasche (1)
- Modellierung (1)
- Modifikation von Biokeramiken (1)
- Molecular Docking (1)
- Molecular modelling (1)
- Molekular Modeling (1)
- Molekulardynamik-Simulationen (1)
- Molekulardynamiksimulationen (1)
- Molekulargenetik (1)
- Mometasone furoate (1)
- Mometasonfuroat (1)
- Monocyten (1)
- Monodisperse PDMS (1)
- Monodisperses System (1)
- Monoklonaler Antikörper (1)
- Monomere (1)
- Monozyt (1)
- Monozyten (1)
- Monte Carlo Simulation (1)
- Monte Carlo simulation (1)
- Mucorales (1)
- Mucormycosis (1)
- Mucus (1)
- Mukovisdizose (1)
- Mukoviszidose (1)
- Multidimensionale Skalierung (1)
- Multidrugresistant (1)
- Muscarinic receptor (1)
- Muscarinischer Rezeptor (1)
- Muskelatrophie (1)
- Mutagenitätstest (1)
- Mutationsfrequenz (1)
- Mutationsrate (1)
- Mykobakterien (1)
- Mykotoxine (1)
- Myositis (1)
- N-Acyl-Ethanolaminphosphate (1)
- N-Demethylierung (1)
- N-Glykane (1)
- N-demethylation (1)
- NACE (1)
- NIR-Spektroskopie (1)
- NMR (1)
- NMR Spektroskopie (1)
- NO-sensitive Guanylyl-Cyclase (1)
- NO-sensitive guanylyl cyclase (1)
- NOX-Inhibitoren (1)
- Nahordnung (1)
- Nanaomaterialien (1)
- Nanohärte (1)
- Nanoindentation (1)
- Nanomaterialien (1)
- Nanopartikelsynthese (1)
- Naphthalimide (1)
- Naphthalinderivate (1)
- Naphthaline (1)
- Naproxen (1)
- Natural product hybrids (1)
- Nature-Insipired Synthesis (1)
- Naturidentischer Aromastoff (1)
- Nebenwirkung (1)
- Netzbogenlänge (1)
- Neuroprotection (1)
- Nichtsteroidales Antiphlogistikum (1)
- Nierenfunktion (1)
- Nipah virus (1)
- Nipha-Virus (1)
- Nuclear Receptor (1)
- Nucleinbasen (1)
- Nukleäre Rezeptoren (1)
- O157 (1)
- ONJ (1)
- ORL1 (1)
- Oberflächenbelegung (1)
- Oberflächenfunktionalisierung (1)
- Oberflächenrauhigkeit (1)
- Olivenöl (1)
- Opiatrezeptor (1)
- Opioide (1)
- Opioids (1)
- Oral Fluid (1)
- Orale Antidiabetika (1)
- Orale Applikation (1)
- Organische Sulfide (1)
- Organischer Kationentransporter (1)
- Osmunda regalis (1)
- Osteoporose (1)
- Outflow funnel (1)
- Outlier Detection (1)
- Outlier-Identifizierung (1)
- Oxidativer Stress (1)
- PDGF (1)
- PDGFR (1)
- PET (1)
- PFG-NMR-Spektroskopie (1)
- PI3K/Akt/mTor pathway (1)
- PKC (1)
- PPIase (1)
- PPIase-Aktivität (1)
- PROTAC (1)
- Pachyrhizus erosus (1)
- Paeonia (1)
- Paraffin (1)
- Parameter Quality Oil (1)
- Parenteral (1)
- Pathogenität (1)
- Patulin (1)
- Pektine (1)
- Peptidomimetikum (1)
- Peptidsynthese (1)
- Perfusion (1)
- Perizyten (1)
- Peroxidzahl (1)
- Pflanzen (1)
- Pflanzenextrakt (1)
- Pflanzenextrakte (1)
- Pflanzeninhaltsstoff (1)
- Phachyrhizus erosus (1)
- Pharmacology (1)
- Pharmacy (1)
- Pharmakometrie (1)
- Pharmazeutische Betreuung (1)
- Pharmazeutische Chemie (1)
- Phase separation (1)
- Phase solubility (1)
- Phenolcarbonsäuren (1)
- Phenolic acids (1)
- Phenylethylamine (1)
- Phosphate (1)
- Phosphoantigene (1)
- Phosphor (1)
- Phosphorylierung (1)
- Phytopathogene (1)
- Phytopathogene Pilze (1)
- Phytopharmakon (1)
- Pilocarpin (1)
- Pilokarpin (1)
- Pinus maritima (1)
- Pipecolinsäurederivate (1)
- Piperedinderivate (1)
- Piperidin (1)
- Pitot-Rohr (1)
- Plant extracts (1)
- Plants (1)
- Plasmaproteinbindung (1)
- Plasmaproteine (1)
- Plasmodien (1)
- Plasmodium (1)
- Platelet-derived Growth Factor (1)
- Point-of-Care-testing (1)
- Pollen (1)
- Poly(2-oxazolin) (1)
- Poly(ethylenglykol) (1)
- Poly(glycerol) (1)
- Polyaminstoffwechsel (1)
- Polychlorierte Biphenyle (1)
- Polydimethylsiloxan (1)
- Polygener Risikoscore (1)
- Polyglycerol (1)
- Polymer-Biokonjugate (1)
- Polymilchsäure (1)
- Polyphenol (1)
- Poorly water-soluble drug (1)
- Positronen-Emissions-Tomographie (1)
- Posttranslational modification (1)
- Posttranslationale Änderung (1)
- Potassium channel (1)
- Praziquantel (1)
- Prickly Pear (1)
- Probenaufarbeitung (1)
- Propenderivate (1)
- Prostaglandine (1)
- Prostaglandinsynthase (1)
- Protease Inhibitoren (1)
- Protease Inhibitors (1)
- Protease inhibitors (1)
- Protease-Inhibitor (1)
- Proteaseinhibitoren (1)
- Proteasen (1)
- Protein Expression (1)
- Protein crystal (1)
- Protein-Ligand Bindung (1)
- Proteinkinase C (1)
- Proteolysis-Targeting-Chimera (1)
- Proteomics (1)
- Protic Ionic Liquids (1)
- Protozoen (1)
- Präamplifizierung (1)
- Prämix (1)
- Prävention (1)
- Pseudodistomin C (1)
- Pseudomonas frederiksbergensis (1)
- Psychopharmakon (1)
- Pulmonale Applikation (1)
- Pulmonary delivery (1)
- Purity Control (1)
- Purity control (1)
- Pyridin (1)
- Pyrimidinone (1)
- Pyroglutaminsäure (1)
- Pyrrolizidinalkaloid-N-Oxid (1)
- Pyrrolizidinalkaloide (1)
- Q-T-Verlängerung (1)
- QSPR (1)
- QSPR-Modeling (1)
- QTc-Verlängerung (1)
- Quality ccontrol (1)
- Quantifizierung (1)
- Quantitative 1H NMR (1)
- Quantitative structure-property relationship modeling (QSPR) (1)
- Quercetin (1)
- Quercetinglucuronide (1)
- Quetiapin (1)
- Quinolone Amides (1)
- Quinolone amides (1)
- RESP model (1)
- RMCA (1)
- RNA degradation (1)
- Radikal (1)
- Radikalfänger (1)
- Radioindikator (1)
- Radiopharmaka (1)
- Radiosynthese (1)
- Raman-Spektroskopie (1)
- Raucher (1)
- ReAsH (1)
- Reaktive Zwischenstufe (1)
- Reaktivitätsstudien (1)
- Receptor Dynamics (1)
- Recovery-Aroma (1)
- Red Fruit Oil (1)
- Red Sea (1)
- Registrierende Härteprüfung (1)
- Reinheit <Motiv> (1)
- Reinheitsprüfung (1)
- Release system (1)
- Renin-Angiotensin-Aldosteron-System (1)
- Reproducibility challenges (1)
- Rezeptor-Kinasen (1)
- Rhizom (1)
- Rifampicin (1)
- Risikobewertung (1)
- Risk Assessment (1)
- Robuvit\(^®\) (1)
- Rohkaffee (1)
- Rucola (1)
- Ruxolitinib (1)
- Röstkaffee (1)
- SAR (1)
- SPECT (1)
- SPM (1)
- Salmeterol (1)
- Salz (1)
- Scanner (1)
- Schafgarbe <Gattung> (1)
- Schellack (1)
- Schimmelpilze (1)
- Schistosomiasis (1)
- Schleim (1)
- Schnelltest (1)
- Schrittmacher (1)
- Schwefelorganische Verbindungen (1)
- Schwein (1)
- Schweine-Caecum-Modell (1)
- Schwämme (1)
- Scoring functions (1)
- Scoring-Funktionen (1)
- Scoringfunktionen (1)
- Seide (1)
- Seiden-Fibroin (1)
- Sekundärmetabolit (1)
- Senecio spp. (1)
- Sensor (1)
- Sensoren (1)
- Sensors (1)
- Serogruppe (1)
- Sesquiterpene lactones (1)
- Sesquiterpenlactonen (1)
- Shelf-life (1)
- Silibinin (1)
- Silibinin ester (1)
- Silk Fibroin (1)
- Silk-Fibroin (1)
- Siloxane (1)
- Simulation (1)
- Sitagliptin (1)
- Site-specific protein conjugation (1)
- Solanum tuberosum (1)
- Solubility (1)
- Sorafenib (1)
- Sorbitolfermentierer (1)
- Spannungskontrollierter Ionenkanal (1)
- Species Differences (1)
- Spectrofluorimetry (1)
- Speichel (1)
- Speziesunterschiede (1)
- Sphingosin (1)
- Spiropiperidine (1)
- Spray drying (1)
- Springs and Parachutes (1)
- Sprühtrocknung (1)
- Spumaviren (1)
- Squalen (1)
- Stabilitätsstudien (1)
- Staphylococcus (1)
- Statine (1)
- Stenotrophomonas maltophilia (1)
- Stereochemie (1)
- Stereoselektiv (1)
- Sternpolymere (1)
- Stickstoffmonoxid-Synthase (1)
- Stickstoffoxide (1)
- Stoffbilanz (1)
- Strawberry (1)
- Streptomyces axinellae (1)
- Streptomycin (1)
- Strukturaufklärungen (1)
- Strukturoptimierung (1)
- Strychnin (1)
- Strychnosalkaloide (1)
- Strömung (1)
- Strömungsverhalten (1)
- Subtraktionsmethoden (1)
- Subtypselektivität (1)
- Sulfatkonjugate (1)
- Sulfonamide (1)
- Sulfonyldiazomethan (1)
- Sulfoxidation (1)
- Synthetische Biologie (1)
- Sythese (1)
- T cell (1)
- T lymphocytes (1)
- T-Lymphoblastomzellen (1)
- T-Lymphozyt (1)
- T-Lymphozyten (1)
- T-Zell-Leukämie (1)
- T-shaped π-π stacking (1)
- T-shaped π–π stacking (1)
- TCDD (1)
- TDDFT (1)
- TDM (1)
- TGF-β3 (1)
- TRESK (1)
- TRI (1)
- Tabakrauch (1)
- Tabletten (1)
- Tacrin (1)
- Tandem Mass Spectrometry (1)
- Tandem-Wittig-1 (1)
- Tanzania (1)
- Teilchen (1)
- Terpene (1)
- Terphenyl Derivate (1)
- Terphenylderivate (1)
- Tetrachlormethan (1)
- Tetracystein-Motive (1)
- Tetracystein-Motivee (1)
- Tetrahydro-15aH-azocino[1 (1)
- Tetrahydro[1 (1)
- Tetrahydrochinazoline (1)
- Thalidomid (1)
- Therapeutic Drug Monitoring (1)
- Therapeutikum (1)
- Therpeutisches Drug Monitoring (1)
- Thiazolidindione (1)
- Thin-layer chromatography (1)
- Thiolase (1)
- Tierversuche (1)
- Timolol (1)
- Toll-like-Rezeptoren (1)
- Tongue (1)
- Toxicokinetics (1)
- Toxikokinetik (1)
- Tracer (1)
- Transgene Tiere (1)
- Traubensilberkerze (1)
- Trennung (1)
- Trichter (1)
- Trimebutin (1)
- Trockenblutanalytik (1)
- Tropenkrankheit (1)
- Trypanosoma brucei brucei (1)
- Trypanosoma cruzi (1)
- Tuberculosis (1)
- Tumorsuppressor-Gen (1)
- Typanosoma (1)
- Tyrosinase (1)
- UHPLC (1)
- UHPLC-ESI-MS/MS (1)
- UV Schutzen (1)
- UV Schuzen (1)
- Ugi-Reaktion (1)
- Ugi-azide reaction (1)
- Universität Würzburg. Lehrstuhl für Pharmazeutische Technologie und Biopharmazie (1)
- Unterernährung (1)
- V. wallichii (1)
- Vaccinium myrtillus <Homöopathie> (1)
- Van-der-Waals-Kraft (1)
- Vascularisation (1)
- Verderb (1)
- Verfügbarkeit (1)
- Vernetzung <Chemie> (1)
- Verunreinigugsprofil (1)
- Verunreinigungen (1)
- Virtual Screening (1)
- Virusrezeptor (1)
- W84 (1)
- Wachstumshemmung (1)
- Wanderratte (1)
- Wassereinflüsse (1)
- Weakly chromophore impurities (1)
- West Africa (1)
- Wirkstoff-Rezeptor-Bindung (1)
- Wissenschaftliches Arbeiten (1)
- Wittig-reaction (1)
- Wurmmittel (1)
- Würzburg / Sonderforschungsbereich Erkennung (1)
- Xanomeline (1)
- Xanthinoxidase (1)
- Xenobiotikum (1)
- Zelloberfläche (1)
- Zellwand (1)
- Zellzyklus (1)
- Zentralnervensystem (1)
- Zerkleinerungsverhalten (1)
- Ziest (1)
- Zigarettenrauch (1)
- Zucker (1)
- Zuckerphosphat (1)
- Zugpannung (1)
- Zugspannungstester (1)
- Zunge (1)
- Zuordnung (1)
- Zygosaccharomyces (1)
- Zygosaccharomyces rouxii (1)
- Zytotoxizität (1)
- \(^{1}\)HNMR (1)
- abiotische (1)
- absolute bioavailability (1)
- absorption (1)
- acebutolol (1)
- acetic acid (1)
- acetones (1)
- acetonitrile (1)
- acetylcholinesterase (1)
- acetylcholinesterase inhibitors (1)
- acid value (1)
- acids (1)
- activation (1)
- active pharmaceutical ingredient (1)
- active pharmaceutical ingredients (1)
- acylated quercetin-tri-glucosides (1)
- additive manufacturing (1)
- adduct (1)
- adipose tissue (1)
- adipose tissue engineering (1)
- adolescents (1)
- advanced drug delivery system (1)
- afatinib (1)
- affinity (1)
- agar diffusion test (1)
- agomelatine (1)
- air humidity (1)
- aldehydes (1)
- alignment (1)
- alignment-free (1)
- alignment-frei (1)
- alkylpyrazines (1)
- allergic rhinitis (1)
- allostere Modulation (1)
- allosterischer Effektor (1)
- alpha Glucosidase (1)
- alpha-Dioxygenase (1)
- alpha-Oxidation (1)
- alpha-Sekretase (1)
- alpha-dioxygenase (1)
- alpha-oxidation (1)
- alzheimer's disease (1)
- amber codon suppression (1)
- amber light (1)
- aminopeptidase N (1)
- ammonium compounds (1)
- amorph (1)
- amorphous (1)
- amorphous solid dispersion (1)
- ampicillin (1)
- amyloid beta (1)
- amyloid-β (Aβ) (1)
- anandamide (1)
- angiogenesis (1)
- angiotensin II type 1 receptor (1)
- animal studies (1)
- anisotropy (1)
- anthocyanin (1)
- anthocyans (1)
- anti-infectives (1)
- anti-inflammatory activity (1)
- anti-inflammatory cytokines (1)
- anti-proliferative effects (1)
- anti-protease (1)
- anti-schistosomal activity (1)
- anti-trypanosomal (1)
- antibacterial activity (1)
- antibacterials (1)
- antibiotic bone concentration (1)
- antifungal (1)
- antifungal drug (1)
- antiinflammatory (1)
- antimicrobial resistance (1)
- antimicrobial stewardship (1)
- antioxidant (1)
- antiresorptive drug-related osteonecrosis of the jaw (1)
- antiviral agents (1)
- antiviral drugs (1)
- arbutin (1)
- arching (1)
- aroma profile (1)
- aspartic proteases (1)
- asthma (1)
- at-home sampling (1)
- atropine (1)
- autoinjector (1)
- automation (1)
- autophagy (1)
- availability (1)
- aziridin (1)
- aziridine (1)
- baclofen homologues (1)
- beclomethasone (1)
- beta-Oxidation (1)
- beta-lactam (1)
- beta-lactam antibiotics (1)
- beta-oxidation (1)
- betony (1)
- bile (1)
- bile salt (1)
- binding (1)
- binding affinity (1)
- binding analysis (1)
- binding constant (1)
- binding mechanism (1)
- bio-orthogonal chemistry (1)
- bioactivity (1)
- bioassay (1)
- bioavailability (1)
- biocatalysis (1)
- bioceramics (1)
- biochemical simulations (1)
- biocide polyhexamethylene biguanide (1)
- bioconjugation (1)
- biodegradable polymer (1)
- biodiversity (1)
- biohydroxylation (1)
- bioisosterism (1)
- biologics (1)
- biologische Körperflüssigkeiten (1)
- biomaterials (1)
- biophysics (1)
- bioresponsive (1)
- biosensor (1)
- biosynthesis (1)
- biotransformation (1)
- bisphosphonates (1)
- bitopic hybrid ligands (1)
- bitopic ligand (1)
- bitopic ligands (1)
- bivalent hybrid compounds (1)
- black cohosh (1)
- blood brain barrier (1)
- blood plasma (1)
- blueberry (1)
- boat conformation (1)
- bone marrow (1)
- bone penetration (1)
- breakage behaviour (1)
- bridge (1)
- bronchial tissue (1)
- brucei (1)
- bulk powder (1)
- bulk solid (1)
- cAMP (1)
- cDNA-Array (1)
- cDNA-array (1)
- cGMP (1)
- caffeic acid bornyl ester (1)
- calmodulin (1)
- calorimetry (1)
- carbamate (1)
- cardiac innervation imaging (1)
- cardiac neurohormonal system (1)
- cartilage (1)
- cartilage tissue engineering (1)
- catechines (1)
- cathepsin (1)
- cecropia telenitida (1)
- cefotiam (1)
- cell metabolism (1)
- cells (1)
- cerebEND cells (1)
- cerulenin (1)
- chemical crosslinking (1)
- chemically programmable (1)
- chemisch programmierbar (1)
- chemometrics (1)
- chemotherapy (1)
- chenopodium quinoa (1)
- children (1)
- chiral (1)
- chiral recognition (1)
- chiral resolution (1)
- chirale Erkennung (1)
- cholesterol and oxy-cholesterol (1)
- cholinergic system (1)
- cholinesterase (1)
- cholinesterase inhibitors (1)
- cholinesterases inhibitors (1)
- chronic IBD model (1)
- circular dichroism (1)
- cis-2-Buten-1 (1)
- citrus (1)
- clinical pharmacy (1)
- co-delivery (1)
- cocrystal (1)
- cofactors (biochemistry) (1)
- cohesion (1)
- cohesive bulk powder (1)
- cold stress (1)
- colloid (1)
- colon-targeting (1)
- commercial preparations (1)
- complementary medicine (1)
- computational chemistry (1)
- concentrate (1)
- confocal Raman-spectroscopy (1)
- conformational anylysis (1)
- contaminants (1)
- continuous ultrafiltration (1)
- counterfeit drugs (1)
- coupled (1)
- crithidia fasciulata (1)
- crystalline (1)
- crystallization (1)
- cystein (1)
- cystein protease inhibitor QSAR (1)
- cysteine proteases (1)
- cystic fibrosis (1)
- cytochrome P450 enzyme (1)
- cytochrome P450 enzymes, carboxylesterases, glutathione S-transferases (1)
- cytochrome-P-450 (1)
- cytokine modulation (1)
- cytokine production (1)
- dabrafenib (1)
- decafluoroazobezene (1)
- degradation of fatty acids (1)
- dehydration (1)
- deoxyhypusinhydroxylase (1)
- derivates (1)
- derivatisation (1)
- design of experiments (1)
- detector (1)
- diabetes (1)
- dicarbonyl (1)
- differentiation (1)
- diffusion constant (1)
- diketopiperazines (1)
- dimere Liganden (1)
- dimeric ligands (1)
- dimeric strychnine ligands (1)
- dioxins (1)
- discovery (1)
- dissolution (1)
- dissolution rates (1)
- distillation books (1)
- dose individualization (1)
- dose linearity (1)
- dried bilberries (1)
- drug formulation (1)
- drug impurities (1)
- drug metabolism (1)
- drug monitoring (1)
- drug-delivery systems (1)
- dualsteric (1)
- dualsteric ligand (1)
- effector Treg (eTreg) (1)
- efflux pumps (1)
- elastic-plastic properties (1)
- elastischer Eindringmodul (1)
- electroactive (1)
- electrohydrodynamic (1)
- electrophoresis (1)
- electrospun fibers (1)
- emulsions oil-in-water (1)
- enantiodifferentiation (1)
- enantiomer (1)
- enantiomerenrein (1)
- enantiomers (1)
- enantiopure (1)
- enantioselectivity (1)
- encapsulation (1)
- endothelial cell (1)
- enoyl reductase (1)
- enoyl-ACP reductase inhibitors (1)
- enoyl-ACP-reductase (1)
- enterohepatic recirculation (1)
- enzyme kinetics (1)
- enzymes (1)
- ephedrine (1)
- epitope mapping (1)
- epoxides (1)
- erythromycin (1)
- esculentus (1)
- ester value (1)
- ethanol (1)
- ethanolaminphosphate (1)
- ethers (1)
- eugenyl cinnamate (1)
- evaporation based detectors (1)
- evaporationsbasierte Detektoren (1)
- ex vivo (1)
- ex vivo Modell (1)
- ex-chiral-pool synthesis (1)
- exchange reaction (1)
- excipient (1)
- excitotoxicity (1)
- experimental visceral leishmaniasis (1)
- expression (1)
- extra cellular matrix (1)
- extraction (1)
- fatty acid metabolism (1)
- fatty acid methyl ester (1)
- fatty acid synthesis II (1)
- fenoterol (1)
- fermentation (1)
- fermentation alcohols (1)
- field testing (1)
- flame retardants (1)
- flavonoid (1)
- flexibility (1)
- flow (1)
- flow properies (1)
- flow properties (1)
- flow-conditioners (1)
- fluidised bed granulation (1)
- fluorescence (1)
- fluorescence polarization (1)
- fluorescence resonance energy transfer (1)
- fluorescent ligands (1)
- fluorescent probes (1)
- fluorimetric assay (1)
- fluorine-18 (1)
- fluoroquinolone (1)
- fluoroquinolones (1)
- fluticasone propionate (1)
- flux (1)
- foamy virus (1)
- food (1)
- food safety (1)
- formaldehyde (1)
- forms (1)
- formulation development (1)
- fractal dimension (1)
- fractionation (1)
- fragment screening (1)
- fragment-based design (1)
- free energy calculations (1)
- free fatty acids (1)
- free radicals (1)
- fruit juice (1)
- funktionale Präpolymere (1)
- furan (1)
- furanone (1)
- gallotannins (1)
- gamma delta (1)
- gastrointestinal (1)
- gastrointestinal tract (1)
- genetic codon expansion (1)
- genetics (1)
- genotoxicity (1)
- gentamicin (1)
- gentamicin sulfate (1)
- germination (1)
- getrocknete Heidelbeeren (1)
- glidant (1)
- glucocorticoids (1)
- glucos metabolism (1)
- glucose (1)
- glucose lowering (1)
- glutamate receptors (1)
- glutamates (1)
- glycocalyx (1)
- glycolytic flux control (1)
- gprotein (1)
- gradient HPLC–UV (1)
- green coffee beans (1)
- green notes (1)
- gut microbiota; bioactivation; polyphenols; complex carbohydrates; tryptophan (1)
- hMSC-TERT (1)
- halo olefines (1)
- hardness (1)
- head and neck carcinoma (1)
- heart failure (1)
- heat shock response (1)
- hepatotoxicity (1)
- herbal books (1)
- high performance liquid chromatography (1)
- high throughput screening (1)
- high-resolution tandem mass spectrometry (1)
- high-throughput screening (1)
- histamine (1)
- history (1)
- homodimerization (1)
- homology modeling (1)
- honey (1)
- honeybee (1)
- honeybees (1)
- hplc (1)
- human African trypanosomiasis (1)
- human mesenchymal stem cells (1)
- human metabolism (1)
- human nutrition (1)
- human plasma (1)
- human receptor kinetics (1)
- humane mesenchymale Stammzellen (1)
- hybrid ligands (1)
- hybrid molecules (1)
- hydnocarpin (1)
- hydrogels (1)
- hydrogen bonding (1)
- hydrogen bonding mycobacterium tuberculosis (1)
- hydrolysis (1)
- hydroperoxides (1)
- hydrophile Interaktionschromatographie (1)
- hydrophilic interaction chromatography (1)
- hydroxy-dabrafenib (1)
- hypertension (1)
- hypoxia (1)
- hysterectomy (1)
- imaging (1)
- immunomodulatory (1)
- impurity profile (1)
- impurity test (1)
- in vitro dissolution methods (1)
- in vitro dissolution testing (1)
- in vitro-in vivo correlation (1)
- in vitro/in vivo Korrelation (1)
- in vitro/in vivo correlation (1)
- in vivo dissolution (1)
- in-vitro-assays (1)
- inclusion complex (1)
- infectious disease (1)
- influences of water (1)
- information technology (1)
- infusion solutions (1)
- inhibition (1)
- injectable protein formulation (1)
- innate immunity (1)
- interleukin-4 (1)
- intermolecular forces (1)
- intermolekulare Kräfte (1)
- internal transcribed spacer 2 (1)
- interparticular forces (1)
- interpartikuläre Haftkräfte (1)
- interpretable (1)
- interpretierbar (1)
- intestinal availability (1)
- intestinal mucus (1)
- intestinal permeability (1)
- intestinale Verfügbarkeit (1)
- intramolecular Michael addition (1)
- intranasal (1)
- intranasal corticosteroids (1)
- intrinsic metabolism (1)
- invasion (1)
- iodine value (1)
- ion-chromatography (1)
- ionic liquids (1)
- ipratropium bromide (1)
- irreversibel (1)
- irreversible (1)
- irreversible Inhibitoren (1)
- irreversible inhibitors (1)
- isocyanide multicomponent reactions (1)
- isoindolines (1)
- isolated reperfused lung (1)
- isolation (1)
- isomerization (1)
- isoprostaglandin (1)
- isosteviol sodium (1)
- isotopically labelled peptides (1)
- istotope discrimination (1)
- jaw bone (1)
- kappa-B activation (1)
- kasA (1)
- ketamine (1)
- kinase inhibitor (1)
- kinase inhibitors (1)
- konfokale Raman-Spektroskopie (1)
- kontinuierliche Ultrafiltration (1)
- kristallin (1)
- lactams (1)
- laser diffraction analysis (1)
- lattice forces (1)
- lead optimization (1)
- lead structure optimization (1)
- leaves (1)
- levodopa (1)
- ligandenselektive Konformationen (1)
- lignaselective conformations (1)
- linear discriminant analysis (1)
- lipid deterioration (1)
- lipid deterioration markers (1)
- liposomes (1)
- lipoxygenase <5-> (1)
- liquid chromatography electrospray ionization tandem mass spectrometry (1)
- liquid chromatography tandem mass spectrometry (LC-MS/MS (1)
- liquid chromatography-mass spectrometry (1)
- liver (1)
- liver impairment (1)
- lower urinary tract (1)
- lowering lattice forces (1)
- lung (1)
- lung perfusion model (1)
- mRNA level (1)
- mRNA-Spiegel (1)
- maceration (1)
- macroarray (1)
- macrophage (1)
- macrophage infectivity potentiator (1)
- macrophage infectivity potentiator protein (1)
- macrophages (1)
- magnesium stearate (1)
- mammary gland (1)
- mannich reaction (1)
- manufacturer (1)
- marine metagenomics (1)
- marine natural products (1)
- marine organisms (1)
- maritime pine bark extract (1)
- markers of exposure (1)
- mass balance (1)
- matrix metalloproteinases (1)
- measurement of humidity (1)
- meat (1)
- meat products (1)
- mechanistic drug-drug interactions (1)
- mechanistische Arzneistoffinteraktionen (1)
- mechanochemical degradation (1)
- medicine authentication tools (1)
- medieval (1)
- medieval herbal books (1)
- melanoma (1)
- melatonin (1)
- melatonin analogues (1)
- melatonin receptor ligands (1)
- membrane (1)
- metabolic glycoengineering (1)
- metabolic network (1)
- metabolic network model (1)
- metabolic syndrome (1)
- metabolisches Netzwerk (1)
- metabolite (1)
- metabonomics (1)
- metastasis (1)
- method development (1)
- methylanthranilate (1)
- micelles (1)
- microemulsion (1)
- microscopy (1)
- microspheres (1)
- mikroorganisms (1)
- mixed-mode chromatography (1)
- mixing conditions (1)
- mobile apps (1)
- model binding site (1)
- modelling (1)
- modelling of a spiral jet mill (1)
- modified monosaccharides (1)
- molecular biopharmaceutics (1)
- molecular dynamic (1)
- molecular dynamics simulations (1)
- molecular mechanics (1)
- molecular systematics (1)
- molekulares Modellieren (1)
- monoclonal antibodies (1)
- monocyte (1)
- monocytes (1)
- monoklonale Antikörper (1)
- mucin (1)
- multicomponent Ugi-type reaction (1)
- multicomponent drugs (1)
- multiple muyloma (1)
- muscarinic (1)
- muscarinic M1 receptor (1)
- muscarinic acetylcholine receptor (1)
- muscarinic acetylcholine receptors (1)
- mutagenicity (1)
- mutation frequency (1)
- mycobacterium tuberculosis (1)
- mycotoxins (1)
- nano-material (1)
- nanomaterials (1)
- nanoparticle synthesis (1)
- nanoparticles (1)
- naphthalenes (1)
- natural ligands (1)
- natural product (1)
- natural product hybrids (1)
- natürliche Liganden (1)
- nerve agent (1)
- network chain length (1)
- neue Inhibitorklasse (1)
- neue Verunreinigungen (1)
- neuroblastoma cell (1)
- neuroprotective (1)
- neuroprotectivity (1)
- new impurities (1)
- new inhibitor class (1)
- nichtpeptidische Inhibitoren (1)
- nicotinic receptors (1)
- non-chromophore analytes (1)
- non-peptidic inhibitors (1)
- non-racemic (1)
- nonhuman primates (1)
- novel nepetolactone derivative (1)
- nuclear cardiology (1)
- nuclear magnetic resonance spectroscopy (1)
- nucleobases (1)
- oak wood (1)
- oak wood extract (1)
- obtusifolia bertol (1)
- octopamine receptors (1)
- oleanane saponins (1)
- olive oil (1)
- online monitoring system (1)
- opioid ligands (1)
- opioid receptors (1)
- oral anticancer drugs (1)
- oral drug absorption (1)
- oral lyophilisate (1)
- oral microbiome (1)
- orale Bioverfügbarkeit (1)
- ortho-Phthaldialdehyd (1)
- ortho-phthaldialdehyd (1)
- osimertinib (1)
- osteochondral implant (1)
- osteoprosis (1)
- oxidative Stressmarker (1)
- oxidative stress (1)
- oxidative stress marker (1)
- oxime (1)
- oxygen (1)
- oxytosis/ferroptosis (1)
- p-Glykoprotein (1)
- paraffins (1)
- parasite (1)
- parasitic (1)
- parasitär (1)
- paromomycin (1)
- particle (1)
- particle surface (1)
- patch clamp recording (1)
- pectins (1)
- pefloxacin (1)
- pentacyclic triterpene (1)
- peptide sensors (1)
- peptide stapling (1)
- peptidomimetic (1)
- peptidomimetisch (1)
- perfluoroarylation (1)
- peri-implant disease (1)
- permeation (1)
- personalized antimicrobial therapy (1)
- pharmaceutical care (1)
- pharmacodynamic (1)
- pharmacological evaluation (1)
- pharmacology (1)
- pharmacometrics (1)
- pharmacy (1)
- phase-solubility (1)
- phenolic acids (1)
- phenylethylamine (1)
- phosphoantigens (1)
- phosphoglycolate phosphatase (1)
- phosphorus (1)
- phosphorylation (1)
- photocontrol (1)
- photopharmacology (1)
- phylogenetic analysis (1)
- phylogenetic tree (1)
- phylogeny (1)
- phytochemicals (1)
- phytochemistry (1)
- phytomedicine (1)
- phytoneering (1)
- phytopathogens (1)
- pig (1)
- pig-caecum-model (1)
- pipecolic acid derivatives (1)
- piperacillin/tazobactam (1)
- piperidin alcaloids (1)
- piperidines (1)
- pitot tube (1)
- plant extracts (1)
- plants (1)
- plasma protein binding (1)
- plasma proteins (1)
- podophyllotoxin (1)
- pollen (1)
- poly(2-ethyl-2-oxazoline) (1)
- poly(dimethylsiloxane) (1)
- polyamine pathway (1)
- polychlorinated biphenyls (1)
- polyethylenglykole (1)
- polylactid (1)
- polymer drug interaction (1)
- polymer processing (1)
- polymers (1)
- polysorbate 80 (1)
- poor water-soluble drugs (1)
- poorly water soluble (1)
- poorly water soluble drugs (1)
- posaconazole (1)
- positron-emission-tomography (1)
- post-operative recovery (1)
- post-surgery recovery (1)
- postsurgical adhesion (1)
- posttranscriptional modification (1)
- posttranskriptionale Modifikation (1)
- powder (1)
- premix (1)
- pressure (1)
- pressurized microwave‐assisted extraction (1)
- prevention (1)
- principal component analysis (1)
- pro-inflammatory cytokines (1)
- process of solution (1)
- procyanidines (1)
- procyanidins (1)
- profiles (1)
- proliferation (1)
- propionate (1)
- protease inhibition (1)
- protease-sensitive release (1)
- proteasome system (1)
- protein (1)
- protein engineering (1)
- protein ligand interactions (1)
- protein modification (1)
- protein nebulization (1)
- protein therapeutics (1)
- pseudodistomine C (1)
- psidium guajava; (1)
- pulmonal (1)
- pulmonary absorption (1)
- purification (1)
- purity control (1)
- pyridine (1)
- pyridobenzodiazepine (1)
- pyroglutamic acid (1)
- pyrrolizidine alkaloid N-oxide (1)
- pyrrolizidine alkaloids (1)
- qPCR (1)
- quality evaluation (1)
- quantification (1)
- quantitativ (1)
- quantitative (1)
- quantitative 1H NMR (1)
- quantitative NMR spectroscopy (1)
- quantitative analysis (1)
- quantum mechanics (1)
- quercetin (1)
- quercetin glucuronides (1)
- quinolones (1)
- quinone oxidoreductase (1)
- radiosynthesis (1)
- radiotracer (1)
- radiotracer kinetics (1)
- radiotracers (1)
- randomized controlled study (1)
- rat study (1)
- reactive metabolites (1)
- reaktive Metabolite (1)
- receptor (1)
- receptors (1)
- recovery aroma (1)
- red blood cells (1)
- red fruit oil (1)
- relation (1)
- relaxation (1)
- remodeling (1)
- renal cell carcinoma (1)
- renin-angiotensin system (1)
- replica-exchange molecular dynamics (1)
- required hydrophilic–lipophilic balance (1)
- residence time (1)
- resistance (1)
- response surface (1)
- ribosomal RNA (1)
- roast coffee (1)
- rocket salad (1)
- ruxolitinib (1)
- sacha inchi oil (1)
- saponification Value (1)
- saturation transfer difference NMR (1)
- scanner (1)
- scar revision surgery (1)
- schistosmiasis (1)
- schistosoma (1)
- schistosomula (1)
- schwefelhaltige Aromastoffe (1)
- schwer wasserlöslich (1)
- scoring functions (1)
- secondary structure (1)
- secreted aspartic proteases (1)
- secretion (1)
- sekretorische Aspartatproteasen (1)
- sensor (1)
- sensory chewing gums (1)
- serjanic acid (1)
- serum (1)
- shellac (1)
- short-range order (1)
- silk fibroin (1)
- silybin (1)
- simple (1)
- simulated intestinal fluid (1)
- single-molecule microscopy (1)
- sisomicin (1)
- site-specific protein modification (1)
- skin whitening (1)
- smooth muscle (1)
- soil-transmitted helminthiases (1)
- solid dispersion (1)
- solid state NMR spectroscopy (1)
- solid-state NMR spectroscopy (1)
- sorbitol-fermenters (1)
- spectrofluorimetry (1)
- sphingomonads (1)
- spice extracts (1)
- spices (1)
- spiropiperidines (1)
- spray (1)
- squalene (1)
- stability (1)
- steered molecular dynamics (1)
- stereoselective (1)
- sterubin (1)
- strawberry (1)
- streptomyces (1)
- structural elucidation (1)
- structure-based drug design (1)
- structure–activity relationships (1)
- strychnine (1)
- subcutaneous fat layer (1)
- substandard and falsified medicines (1)
- subtractive-methods (1)
- subtype selectivity (1)
- sugar phosphate (1)
- sulfoxidation (1)
- sulfur containing flavour compounds (1)
- sun screening (1)
- surface coverage (1)
- surface functionalization (1)
- surface roughness (1)
- synovial fluid (1)
- system (1)
- tablets (1)
- tacrine (1)
- tandem mass spectrometry (1)
- tandem-Wittig-1 (1)
- tensile strength tester (1)
- tensile strengths (1)
- terphenyl derivatives (1)
- tetromycin (1)
- thalidomide (1)
- therapeutic gases (1)
- therapeutic strategy (1)
- therapeutisches Target (1)
- thermodynamic (1)
- thermodynamics (1)
- thin-layer chromatography (1)
- thymyl cinnamate (1)
- timololmaleate (1)
- tofacitinib (1)
- toll-like receptors (1)
- tongue (1)
- topical treatment (1)
- total synthesis (1)
- toxicity (1)
- track and trace (1)
- trametinib (1)
- transglutaminase (1)
- translationally and rotationally invariant (1)
- translations- und rotationsinvariant (1)
- transport (1)
- treatment regimens (1)
- triacylglycerides (1)
- tropische Infektionskrankheiten (1)
- trypanosoma cruzi (1)
- tuberculosis (1)
- tumor suppressor gene (1)
- two-dimensional (1)
- type 2 diabetes (1)
- tyrosinase (1)
- underutilized legumes (1)
- unnatural amino acid (1)
- unsaturated fatty acids (1)
- unterer Harntrakt (1)
- urolithins (1)
- ursolic acid (1)
- vacuoles (1)
- valsartan (1)
- valtrates (1)
- vascularized fat construct (1)
- velocity (1)
- veterinarians (1)
- veterinary medicine (1)
- vif (1)
- volumetric absorptive micro-sampling (VAMS) (1)
- volumetric absorptive microsampling (1)
- watersolubility (1)
- young’s modulus (1)
- zweidimensional (1)
- HILIC (1)
- Ölsäure (1)
- ß-Carbolinalkaloide, 7-Alkyloxycumarine, Clopidogrel, Paracetamol (1)
- ß-Carboline (1)
- ß-carboline alkaloids, 7-alkyloxycoumarins, clopidogrel, acetaminophen (1)
- ß-carbolines (1)
- β2 - Agonisten (1)
- β2 - agonist (1)
Institute
- Institut für Pharmazie und Lebensmittelchemie (400) (remove)
Sonstige beteiligte Institutionen
- Universität Belgrad, Serbien (2)
- ACC GmbH Analytical Clinical Concepts (1)
- Apotheke, Universitätsklinikum Würzburg (1)
- Bayer AG, Research & Development, Pharmaceuticals, Investigational Toxicology (1)
- Bundesinstitut für Arzneimittel und Medizinprodukte (1)
- Friedrich-Schiller-Universität Jena (1)
- Helmholtz Institute for RNA-based Infection Biology (HIRI), Josef-Schneider-Straße 2/D15, DE-9708 Wuerzburg, Germany (1)
- Helmholtz Institute for RNA-based Infection Biology (HIRI), Josef-Schneider-Straße 2/D15, DE-97080 Wuerzburg, Germany (1)
- IBMP - Institut für Biomedizinische und Pharmazeutische Forschung in Nürnberg-Heroldsberg (1)
- Johns Hopkins School of Medicine (1)
EU-Project number / Contract (GA) number
- 26230120009 (1)
- 296679 (1)
- 314911 (1)
- 701983 (1)
Amber Light Control of Peptide Secondary Structure by a Perfluoroaromatic Azobenzene Photoswitch
(2023)
The incorporation of photoswitches into the molecular structure of peptides and proteins enables their dynamic photocontrol in complex biological systems. Here, a perfluorinated azobenzene derivative triggered by amber light was site‐specifically conjugated to cysteines in a helical peptide by perfluoroarylation chemistry. In response to the photoisomerization (trans→cis) of the conjugated azobenzene with amber light, the secondary structure of the peptide was modulated from a disorganized into an amphiphilic helical structure.
Die Interaktion des onkogenen Transkriptionsfaktors MYCN mit der Ser/Thr Kinase Aurora-A verhindert
dessen Abbau über das Ubiquitin Proteasomsystem indem die Rekrutierung des SCF FbxW7 Komplexes
verhindert wird. Die Kinase nimmt mit der Bindung an MYCN eine aktive Konformation ein und erhält
somit die Fähigkeit zur Kinaseaktivität ohne die sonst notwendige Phosphorylierung von Thr288 oder
die Anwesenheit eines Aktivators wie TPX2. Da hohe MYCN Konzentrationen Tumore wie
Neuroblastome antreiben, ist die Störung der Komplexbildung mit Aurora-A eine valide Strategie zur
Entwicklung von Chemotherapeutika. Einige Inhibitoren von Aurora-A wie Alisertib (MLN8237) sind in
der Lage, eine Konformationsänderung in der Kinase zu verursachen, die mit der Bindung von MYCN
inkompatibel ist und auf diese Weise den Abbau des Transkriptionsfaktors induziert. Da Aurora-A
wichtige Funktionen in der Mitose übernimmt, könnte eine direkte Adressierung des Komplexes anstelle
einer systemischen Inhibition der Kinase vielversprechender sein.
Ziel des Projektes war die Identifizierung von Molekülen, die selektiv an das Interface des
Aurora-A – MYCN Komplexes binden und weiter optimiert werden können, um einen gezielten Abbau
des Transkriptionsfaktors über einen PROTAC Ansatz zu ermöglichen. Virtuelle Screenings und
molekulardynamische Simulationen wurden durchgeführt, um kommerziell erhältliche Verbindungen zu
identifizieren, welche mit einer Bindetasche des Komplexes interagieren, die nur zustande kommt, wenn
beide Proteine miteinander interagieren. Aus einem ersten Set von zehn potentiellen Liganden wurde
für vier eine selektive Interaktion mit dem Protein – Protein Komplex gegenüber Aurora-A oder MYCN
alleine in STD-NMR Experimenten bestätigt. Zwei der Hits besaßen ein identisches Grundgerüst und
wurden als Ausganspunkt für die Optimierung zu potenteren Liganden genutzt. Das Gerüst wurde
fragmentweise vergrößert und in Richtung besserer in-silico Ergebnisse und Funktionalisierung zur
Anbringung von E3-Ligase-Liganden optimiert. Neun dieser Liganden der zweiten Generation wurden
synthetisiert.
Um quantitative Bindungsdaten zu erhalten, wurde ein kovalent verknüpftes Aurora-A – MYCN
Konstrukt entworfen. Die strukturelle und funktionale Integrität wurde in STD-NMR und BLI
Experimenten mit bekannten Aurora-A Inhibitoren bestätigt, sowie in NMR-basierten ATPase Assays.
Zusätzlich konnte die Kristallstruktur des Konstrukts gelöst und damit die Validität des Designs bestätigt
werden. Quantitative Messungen der synthetisierten Moleküle identifizierten HD19S als Hit mit einer
zehnfach höheren Affinität für das Aurora-A – MYCN Konstrukt im Vergleich zu der Kinase allein.
Zusätzlich wurden in-silico Untersuchungen zu PROTACs der Aurora-A Kinase durchgeführt.
Interaktionen zwischen Aurora-A, der E3-Ligase Cereblon und den Liganden wurden modelliert und für
die Erklärung unterschiedlicher Aktivitäten der eingesetzten PROTACs verwendet. Zudem zeigte das
aktivste PROTAC eine hohe Selektivität für Aurora-A gegenüber Aurora-B, obwohl die verwendete
Erkennungseinheit (Alisertib) an beide Aurora-Proteine bindet. Dieser Umstand konnte durch
energetische Analysen von molekulardynamischen Simulationen der ternären Komplexe erklärt werden.
Optimierungsmöglichkeiten für eine effizientere Degradation von Aurora-A durch die PROTACs wurden
basierend auf modifizierten Erkennungseinheiten und verbesserten Linkern untersucht.
Dietary fatty acids serve as objective biomarkers for the estimation of habitual diet mainly because biomarkers are free of memory bias or inaccuracies of food databases. The aim of the present work encompassed the implementation of a gas chromatographical method coupled with a mass spectrometrical and flame-ionization detector for analysis of fatty acid biomarkers in human biospecimens, their analytical determination and statistical evaluation in two different study populations and different biospecimens as well as the elaboration of adverse reactions to food ingredients with special focus on food allergies and food intolerances in the context of a possible implementation into an application for consumer health. The first aim was the identification of potential influence of fatty acid biomarkers on desaturase and elongase indexes (Δ9DI, Δ6DI, Δ5DI and ELOVLI5), which are factors in type 2 diabetes risk, in breast adipose tissue from healthy women. Influence of further variables on respective indexes was also investigated. 40 samples were investigated and potential variables were either collected by questionnaire or determined. Principle component analysis was applied for fatty acid biomarkers (PCdiet1, PCdiet2 and PCdiet3 representative for the dietary intake of vegetable oils/nuts, fish and partially hydrogenated vegetable oils), endogenous estrogens (PCE1) and oxysterols (PCOxy1). Multiple linear regression models were applied. Δ9DI and Δ6DI were influenced non-significantly and significantly negatively by PCdiet2 supporting a putative beneficial effect of vegetable oils and nuts on type 2 diabetes risk factors. ELOVLI5 and Δ5DI were influenced significantly and non-significantly positively by PCdiet1 supporting a putative beneficial effect of fish consumption on type 2 diabetes risk factors. On the other hand, PCdiet1 also significantly and non-significantly positively influenced Δ9DI and Δ6DI supporting a putative adverse effect of fish biomarkers on type 2 diabetes risk factors. The opposing influences of PCdiet1 suggesting an ambivalent role of dietary intake of fish on investigated indexes. Δ6DI was significantly positively influenced by PCdiet3 and number of pregnancies supporting a putative adverse effect of partially hydrogenated vegetable oils and pregnancies on type 2 diabetes risk factors. Lifestyle factors like smoking significantly and non-significantly influenced Δ9DI and Δ6DI putatively adversely. Δ5DI was influenced significantly positively by estrogen active drugs suggesting a putative beneficial effect on type 2 diabetes risk factors. It must be considered that a variation coefficient of up to 0.44 only explained 44% of variance of the respective indexes, suggesting other influencing factors might play a role. The second aim was the implementation of a gas chromatographical method coupled with a mass spectrometrical and flame-ionization detector for analysis of fatty acid biomarkers in human biospecimens. The method was optimized for separation and detection of 40 fatty acids. Mean recovery for tridecanoic acid was x(tridecanoic acid) = 90.51% and for nonadecanoic acid x(nonadecanoic acid) = 96.21%. Thus, there was no significant loss of fatty acids with shorter and longer carbon chains over the extraction process to be expected. Limit of detections were calculated in adipose tissue samples and ranged from 0.007 to 0.077% of the proportion of the respective fatty acid to total fatty acids. The third aim was the investigation if differentiation between breast glandular and adipose tissue had a relevant impact on the analysis of dietary fatty acid biomarkers or if contamination of breast glandular with breast adipose tissue and vice versa was neglectable for the analysis of dietary fatty acid biomarkers. No statistical significant differences were observed for all investigated fatty acid biomarkers (pentadecanoic-, heptadecanoic-, trans palmitoleic-, eicosapentaenoic-, docosahexaenoic-, linoleic and α-linolenic acid) between breast glandular and adipose tissue. Thus, differentiation between breast glandular and adipose tissue seems not to be necessary for the analysis of fatty acids serving as biomarkers for the intake of specific food groups. Potential influence of mixed breast tissue on fatty acid biomarkers analysis seems to be neglectable. The fourth aim was the determination of fatty acid biomarkers in adipose tissue in another study population from healthy participants. 27 adipose tissue samples were analyzed. Milk and ruminant fat biomarkers exhibited proportions of 0.47% for pentadecanoic acid, 0.34% for heptadecanoic acid and 0.25% for trans palmitoleic acid. Fish fatty acid biomarkers revealed proportions of 0.034% for eicosapentaenoic acid and 0.061% for docosahexaenoic acid. The mean proportion of vegetable oils and nuts biomarkers were 9.58% for linoleic acid and 0.48% for α-linolenic acid in all adipose tissues. Principle component analysis was applied for the fatty acid biomarkers to provide objective markers of habitual diet for this study population. PCdiet1 was mainly characterized by pentadecanoic acid, heptadecanoic acid and trans palmitoleic acid and therefore served as a principle component for the dietary intake of milk and ruminant fat. PCdiet2 and PCdiet3 only exhibited pattern for ω3 and ω6 fatty acids but not for dietary intake of specific food groups and could therefore not used as objective marker. PCdiet1, 2 and 3 explained 82.76% of variance. The last aim of this thesis was the elaboration of adverse reactions to food ingredients with special focus on food allergies and food intolerances in the context of a possible implementation into an application for consumer health. Scientific information on adverse reactions to food ingredients and trigger substances was provided in this thesis and possible implementation strategies were evaluated. For food allergens, which have regulatory requirements in the context of labelling, a strategy was elaborated, where it is necessary to provide information on the list of ingredients, the nexus ’contain’ and the respective food allergen as well as information on the name of the product. For food intolerances, which do not have regulatory requirements, limits were shown in the context of the application. If the elaborated food intolerances shall be implemented into the application, a professional dietary concept has to be developed for every food intolerance because of the complexity of the implementation.
As part of the parasympathetic nervous system, muscarinic receptors are involved in the regulation of numerous functions in the human body. However, targeting a specific subtype of muscarinic receptors is challenging due to the high degree of similarity within the binding site of the endogenous neurotransmitter acetylcholine. Therefore, this study focused on the investigation of dualsteric ligands. Such hybrid ligands target the orthosteric acetylcholine binding site and, simultaneously, a distinct allosteric binding site. Since allosteric binding regions show significant structural differences throughout muscarinic receptor subtypes, it was aimed to produce selective ligands by means of combination of two pharmacophores in one molecule. Herein, the thienopyridine derivatives LY2033298 and LY2119620 were chosen as allosteric moieties. Based on literature studies, the investigated allosteric modulators were analyzed in terms of adequate attachment points for the combination with an orthosteric agonist. As orthosteric units, muscarinic superagonist iperoxo, xanomeline, and TMA were applied in this work. Since the distance between orthosteric and allosteric moieties plays a crucial role for dualsteric ligand binding, the linker chain length was also varied. Pharmacological investigations of the synthesized hybrid ligands were perfomed via FRET- and BRET-assay measurements.
Azobenzene derivatives with activity against drug‐resistant Candida albicans and Candida auris
(2023)
Increasing resistance against antimycotic drugs challenges anti‐infective therapies today and contributes to the mortality of infections by drug‐resistant Candida species and strains. Therefore, novel antifungal agents are needed. A promising approach in developing new drugs is using naturally occurring molecules as lead structures. In this work, 4,4'‐dihydroxyazobenzene, a compound structurally related to antifungal stilbene derivatives and present in Agaricus xanthodermus (yellow stainer), served as a starting point for the synthesis of five azobenzene derivatives. These compounds prevented the growth of both fluconazole‐susceptible and fluconazole‐resistant Candida albicans and Candida auris strains. Further in vivo studies are required to confirm the potential therapeutic value of these compounds.
The aim of this study was to determine the potential of some Ghanaian underutilized legumes in helping to reduce the problems of poverty, hunger and malnutrition among the vulnerable group of the Ghanaian population. The study looked into the functional properties, fat and fatty acid distribution, raffinose, sucrose, glucose, fructose, calcium, magnesium, sodium, potassium, iron, copper, manganese, zinc, cyanide and isoflavone contents of raw and processed seed flours of Cajanus cajan, Canavalia ensiformis, Canavalia gladiata, Mucuna pruriens, Parkia biglobosa, Phaseolus lunatus and Vigna subterranea. The parameters mentioned above were also determined for raw fruit flour of Dialium guineense. In addition to these, the study also looked into the crude protein and starch contents of the raw and processed seed flours of Canavalia gladiata, Parkia biglobosa and Vigna subterranea. The obtained results suggest that the legumes may have untapped potential, which may be exploited to help assist in reducing hunger, malnutrition and poverty in Ghana. Results of the functional properties reveal that the legumes may serve useful roles in various food products. For instance, velvet tamarind (Dialium guineense) flour may be useful in infant food formulations because of it high solubility and low bulk density. African Locust bean (Parkia biglobosa) flour had the highest fat content among the studied flours, recording a fat content of approximately 14%. It may therefore be economical to express the oil and use the oil as an edible oil or for industrial applications for products such as soaps, shampoos, paints, etc. This means the properties of the oil of African Locust bean flour need to be studied to know the uses of the oil. Unsaturated fatty acids in the cis configuration formed more than 50% of the fatty acids in all the legumes. This observation coupled with the low sodium content of all the legumes suggest that these legumes may be suitable for consumption to prevent cardiovascular diseases. The daily nutrient needs of individuals can be met by the consumption of the appropriate amounts of these legumes. For example, 375.25 g of processed velvet beans (Mucuna pruriens) flour may be able to meet the adequate intake (AI) of 350 mg/day magnesium for adult males.
In all the projects presented, it is evident that the selection of suitable separation conditions is only one side of the coin. Equally crucial in the development of methods for the quality assessment of APIs/drugs is the right detection system.
The application of CAD as an alternative to UV detection at low wavelength of the two weak chromophore main degradation products of the very polar, zwitterionic API carbocisteine requires the volatility of the mobile phase. Therefore, as a substitute for the non-volatile ion pairing reagent tetrabutylammonium hydroxide (TBAOH), six different volatile alkylamines as well as a RP/SAX mixed-mode column were evaluated. The best selectivity and separation performance comparable to TBAOH was achieved with the RP/SAX column and a mixture of formic acid and trifluoroacetic acid. For the simultaneous optimisation of the evaporation temperature of the CAD as a function of two chromatographic parameters, a central composite design was chosen and the “desirability function” was subsequently applied for modelling. In addition, column bleeding was investigated with a second RP/SAX column (different batch) with the result that the acetonitrile percentage had to be adjusted and preconditioning by injection of concentrated samples is essential. The final mixed-mode method was finally validated with both columns according to the ICH Q2 (R1) guideline.
Based on this, an MS-compatible method was developed with little effort using an identical RP/SAX column in UPLC dimension for the untargeted analysis by HRMS of two carbocisteine-containing prototype syrup formulations. For a comprehensive characterisation, HRMS and MS/HRMS data were recorded simultaneously by information dependent acquisition mode. Based on the exact masses, isotope patterns and an in silico plausibility check of the fragment spectra, the prediction of the structures of the unknown impurities was possible. In both syrup samples, which had been stored for nine months at 40 °C and 75 % r.h., two additional impurities of carbocisteine (i.e. lactam of the sulfoxides and disulphide between cysteine and thioglycolic acid) were identified by comparison with the corresponding prototype placebo samples using general unknown comparative screening. In addition, the formation of Maillard products by binary mixtures with 13C-labelled sugars was revealed in the sucrose-containing formulation.
For the promising hyphenation of the UV detector with the CAD for the simultaneous detection of all UV-active impurities of the cholesterol-lowering drug simvastatin and the only weak chromophore dihydrosimvastatin, the Ph. Eur. method had to be adapted. Besides replacing phosphoric acid with trifluoroacetic acid, the gradient also had to be adjusted and a third critical peak pair was observed. Based on validation experiments (according to the ICH Q2 (R1) guideline), the suitability of the CAD for sensitive detection (LOQ = 0.0175 % m/m) was proven.
To further investigate the robustness of the adapted method and CAD, a Plackett-Burman design was chosen. None of the factors had a statistically significant effect on the S/N of the CAD in the ranges tested. Regarding the three critical peak pairs, on the other hand, the factors to be controlled were statistically established, so that a targeted correction is possible if the system suitability test is not passed. The idea of employing a hyphenated UV-CAD system was finally applied to the structurally closely related lovastatin and its specified impurity dihydrolovastatin. Here, the CAD showed a significantly better S/N compared to the compendial UV detection at 200 nm.
The suitability of CAD for the analysis of non-volatile fatty acids in polysorbate 80 (PS80) as favourable alternative to the Ph. Eur. GC method (no time-consuming, error-prone and toxic derivatisation) has already been demonstrated. The aim of this project was therefore to develop a robust method with a focus on the AQbD principles, which can be used for the analysis of other excipients with similar fatty acid composition. After the definition of the analytical target profile and a risk assessment by means of an Ishikawa diagram, a suitable C18 column and the chromatographic framework conditions (formic acid concentration and initial/final gradient conditions) were selected after only few preliminary runs. The remaining critical method parameters were then investigated with the help of DoE and RSM. Using the obtained model equations, Monte Carlo simulations were performed to create the method operable design region as a region of theoretical robustness. After validation according to ICH Q2 (R1), the fatty acid composition of a magnesium stearate batch was successfully analysed as a further application example in addition to PS80.
The CAD was able to prove its potential in all the issues investigated in the context of this doctoral thesis. As a cost-effective alternative compared to MS instruments, it thus closes a gap in the quality assessment of APIs or excipients without a suitable chromophore. The easy method transfer to (HR)MS instruments also allows for a unique degree of sample characterisation through untargeted approaches in case of new impurities. For resource- and time-efficient work, the possibilities and limitations of software tools for method development and data evaluation as well as the application of risk-based approaches such as AQbD should also be considered.
Oral antineoplastic drugs are an important component in the treatment of solid tumour diseases, haematological and immunological malignancies. Oral drug administration is associated with positive features (e.g., non-invasive drug administration, outpatient care with a high level of independence for the patient and reduced costs for the health care system). The systemic exposure after oral intake however is prone to high IIV as it strongly depends on gastrointestinal absorption processes, which are per se characterized by high inter-and intraindividual variability. Disease and patient-specific characteristics (e.g., disease state, concomitant diseases, concomitant medication, patient demographics) may additionally contribute to variability in plasma concentrations between individual patients. In addition, many oral antineoplastic drugs show complex PK, which has not yet been fully investigated and elucidated for all substances. All this may increase the risk of suboptimal plasma exposure (either subtherapeutic or toxic), which may ultimately jeopardise the success of therapy, either through a loss of efficacy or through increased, intolerable adverse drug reactions. TDM can be used to detect suboptimal plasma levels and prevent permanent under- or overexposure. It is essential in the treatment of ACC with mitotane, a substance with unfavourable PK and high IIV. In the current work a HPLC-UV method for the TDM of mitotane using VAMS was developed. A low sample volume (20 µl) of capillary blood was used in the developed method, which facilitates dense sampling e.g., at treatment initiation. However, no reference ranges for measurements from capillary blood are established so far and a simple conversion from capillary concentrations to plasma concentrations was not possible. To date the therapeutic range is established only for plasma concentrations and observed capillary concentrations could not be reliable interpretated.The multi-kinase inhibitor cabozantinib is also used for the treatment of ACC. However, not all PK properties, like the characteristic second peak in the cabozantinib concentration-time profile have been fully understood so far. To gain a mechanistic understanding of the compound, a PBPK model was developed and various theories for modelling the second peak were explored, revealing that EHC of the compound is most plausible. Cabozantinib is mainly metabolized via CYP3A4 and susceptible to DDI with e.g., CYP3A4 inducers. The DDI between cabozantinib and rifampin was investigated with the developed PBPK model and revealed a reduced cabozantinib exposure (AUC) by 77%. Hence, the combination of cabozantinib with strong CYP inducers should be avoided. If this is not possible, co administration should be monitored using TDM. The model was also used to simulate cabozantinib plasma concentrations at different stages of liver injury. This showed a 64% and 50% increase in total exposure for mild and moderate liver injury, respectively.Ruxolitinib is used, among others, for patients with acute and chronic GvHD. These patients often also receive posaconazole for invasive fungal prophylaxis leading to CYP3A4 mediated DDI between both substances. Different dosing recommendations from the FDA and EMA on the use of ruxolitinib in combination with posaconazole complicate clinical use. To simulate the effect of this relevant DDI, two separate PBPK models for ruxolitinib and posaconazole were developed and combined. Predicted ruxolitinib exposure was compared to observed plasma concentrations obtained in GvHD patients. The model simulations showed that the observed ruxolitinib concentrations in these patients were generally higher than the simulated concentrations in healthy individuals, with standard dosing present in both scenarios. According to the developed model, EMA recommended RUX dose reduction seems to be plausible as due to the complexity of the disease and intake of extensive co-medication, RUX plasma concentration can be higher than expected.
Characterization of binding properties of ephedrine derivatives to human alpha-1-acid glycoprotein
(2023)
Most drugs, especially those with acidic or neutral moieties, are bound to the plasma protein albumin, whereas basic drugs are preferentially bound to human alpha-1-acid glycoprotein (AGP). The protein binding of the long-established drugs ephedrine and pseudoephedrine, which are used in the treatment of hypotension and colds, has so far only been studied with albumin. Since in a previous study a stereoselective binding of ephedrine and pseudoephedrine to serum but not to albumin was observed, the aim of this study was to check whether the enantioselective binding behavior of ephedrine and pseudoephedrine, in addition to the derivatives methylephedrine and norephedrine, is due to AGP and to investigate the influence of their different substituents and steric arrangement. Discontinuous ultrafiltration was used for the determination of protein binding. Characterization of ligand-protein interactions of the drugs was obtained by saturation transfer difference nuclear magnetic resonance spectroscopy. Docking experiments were performed to analyze possible ligand-protein interactions. The more basic the ephedrine derivative is, the higher is the affinity to AGP. There was no significant difference in the binding properties between the individual enantiomers and the diastereomers of ephedrine and pseudoephedrine.
Alzheimer´s disease (AD) is a neurodegenerative disease and the most common form of dementia with still no preventive or curative treatment. Besides several risk factors, age is one of the major risks for AD and with an aging society, there is an urgent need for disease modifying agents. The strategy to address only one target within the intertwined network of AD failed so far.
Natural products especially the phytochemical flavonoids, which are poly-phenolic natural products, have shown great potential as disease modifying agents against neurodegenerative disorders like Alzheimer´s disease (AD) with activities even in vivo. Flavonoids are produced by many plants and the native Californian plant Eriodictyon californicum is particularly rich in flavonoids. One of the major flavonoids of E. californicum is sterubin, a very potent agent against oxidative stress and inflammation, two hallmarks and drivers of AD and neurodegeneration. Herein, racemic sterubin was synthesized and separated into its pure (R)- and (S)-enantiomer by chiral HPLC. The pure enantiomers showed comparable neuroprotection in vitro with no significant differences. The stereoisomers were configurationally stable in methanol, but fast racemization was observed in culture medium. Moreover, the activity of sterubin was investigated in vivo, in an AD mouse model. Sterubin showed a significant positive impact on short- and long-term memory at low dosages.
A promising concept for the increase of activity of single flavonoids is hybridization with aromatic acids like cinnamic or ferulic acids. Hybridization of the natural products taxifolin and silibinin with cinnamic acid led to an overadditive effect of these compounds in phenotypic screening assays related to neurodegeneration and AD. Because there are more potent agents as taxifolin or silibinin, the hybrids were further developed, and different flavonoid cinnamic acid hybrids were synthesized. The connection between flavonoids and cinnamic acid was achieved by an amide instead of a labile ester to improve the stability towards hydrolysis to gain better “druggability” of the compounds. To investigate the oxidation state of the C-ring of the flavonoid part, the dehydro analogues of the respective hybrids were also synthesized. The compounds show neuroprotection against oxytosis, ferroptosis and ATP-depletion in the murine hippocampal cell line HT22. While no overall trend within the flavanones compared to the flavones could be assigned, the taxifolin and the quercetin derivative were the most active compounds in course of all assays. The quercetin derivate even shows greater activity than the taxifolin derivate in every assay. As desired no hydrolysis product was found in cellular uptake experiments after 4h, whereas different metabolites were found. The last part of this work focused on synthetic bioisoteres of the natural product curcumin. Due to the drawbacks of curcumin and flavonoids arising from poor pharmacokinetics, rapid metabolism and sometimes instability in aqueous medium, we have examined the biological activity of azobenzene compounds designed as bioisoteres of curcumin, carrying the pharmacophoric catechol group of flavonoids. These bioisosteres exceeded their parent compounds in counteracting intracellular oxidative stress, neuroinflammation and amyloid-beta aggregation. By incorporating an azobenzene moiety and the isosteric behaviour to the natural parent compounds, these compounds may act as molecular tools for further investigation towards the molecular mode of action of natural products.