TY  - JOUR
A1  - Güntzel, Paul
A1  - Schilling, Klaus
A1  - Hanio, Simon
A1  - Schlauersbach, Jonas
A1  - Schollmayer, Curd
A1  - Meinel, Lorenz
A1  - Holzgrabe, Ulrike
T1  - Bioinspired Ion Pairs Transforming Papaverine into a Protic Ionic Liquid and Salts
JF  - ACS Omega
N2  - Microbial, mammalian, and plant cells produce and contain secondary metabolites, which typically are soluble in water to prevent cell damage by crystallization. The formation of ion pairs, for example, with carboxylic acids or mineral acids, is a natural blueprint to maintain basic metabolites in solution. Here, we aim at showing whether the mostly large carboxylates form soluble protic ionic liquids (PILs) with the basic natural product papaverine resulting in enhanced aqueous solubility. The obtained PILs were characterized by H-1-N-15 HMBC nuclear magnetic resonance (NMR) and in the solid state using X-ray powder diffraction, differential scanning calorimetry, and dissolution measurements. Furthermore, their supramolecular pattern in aqueous solution was studied by means of potentiometric and photometrical solubility, NMR aggregation assay, dynamic light scattering, zeta potential, and viscosity measurements. Thereby, we identified the naturally occurring carboxylic acids, citric acid, malic acid, and tartaric acid, as being appropriate counterions for papaverine and which will facilitate the formation of PILs with their beneficial characteristics, like the improved dissolution rate and enhanced apparent solubility.
KW  - solubility
KW  - transport
KW  - strategy
KW  - drugs
KW  - forms
KW  - acids
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230265
VL  - 5
IS  - 30
ER  - 
TY  - JOUR
A1  - Raschig, Martina
A1  - Ramírez‐Zavala, Bernardo
A1  - Wiest, Johannes
A1  - Saedtler, Marco
A1  - Gutmann, Marcus
A1  - Holzgrabe, Ulrike
A1  - Morschhäuser, Joachim
A1  - Meinel, Lorenz
T1  - Azobenzene derivatives with activity against drug‐resistant Candida albicans and Candida auris
JF  - Archiv der Pharmazie
N2  - 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.
KW  - antifungal drug
KW  - azobenzenes
KW  - Candida auris
KW  - Candida albicans
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312295
VL  - 356
IS  - 2
ER  - 
TY  - JOUR
A1  - Masota, Nelson E.
A1  - Ohlsen, Knut
A1  - Schollmayer, Curd
A1  - Meinel, Lorenz
A1  - Holzgrabe, Ulrike
T1  - Isolation and characterization of galloylglucoses effective against multidrug-resistant strains of Escherichia coli and Klebsiella pneumoniae
JF  - Molecules
N2  - The search for new antibiotics against multidrug-resistant (MDR), Gram-negative bacteria is crucial with respect to filling the antibiotics development pipeline, which is subject to a critical shortage of novel molecules. Screening of natural products is a promising approach for identifying antimicrobial compounds hosting a higher degree of novelty. Here, we report the isolation and characterization of four galloylglucoses active against different MDR strains of Escherichia coli and Klebsiella pneumoniae. A crude acetone extract was prepared from Paeonia officinalis Linnaeus leaves, and bioautography-guided isolation of active compounds from the extract was performed by liquid–liquid extraction, as well as open column, flash, and preparative chromatographic methods. Isolated active compounds were characterized and elucidated by a combination of spectroscopic and spectrometric techniques. In vitro antimicrobial susceptibility testing was carried out on E. coli and K. pneumoniae using 2 reference strains and 13 strains hosting a wide range of MDR phenotypes. Furthermore, in vivo antibacterial activities were assessed using Galleria mellonella larvae, and compounds 1,2,3,4,6-penta-O-galloyl-β-d-glucose, 3-O-digalloyl-1,2,4,6-tetra-O-galloyl-β-d-glucose, 6-O-digalloyl-1,2,3,4-tetra-O-galloyl-β-d-glucose, and 3,6-bis-O-digalloyl-1,2,4-tri-O-galloyl-β-d-glucose were isolated and characterized. They showed minimum inhibitory concentration (MIC) values in the range of 2–256 µg/mL across tested bacterial strains. These findings have added to the number of known galloylglucoses from P. officinalis and highlight their potential against MDR Gram-negative bacteria.
KW  - antimicrobial resistance
KW  - Enterobacteriaceae
KW  - Paeonia
KW  - gallotannins
KW  - isolation
KW  - structural elucidation
KW  - Escherichia coli
KW  - Klebsiella pneumoniae
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-286179
SN  - 1420-3049
VL  - 27
IS  - 15
ER  -