@article{KrannichThereseBroscheitetal.2012,
  author    = {Krannich, Jens-Holger and Therese, Tobias and Broscheit, Jens and Leyh, Rainer and M{\"u}llges, Wolfgang},
  title     = {Diabetes severely affects attentional performance after coronary artery bypass grafting},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75320},
  year      = {2012},
  abstract  = {Background: Diabetes is a risk factor for (micro) vascular damage of the brain, too. Therefore cognitive performance after coronary artery bypass grafting may be hypothesized worse in diabetics. To avoid observational errors a reliable tool for testing attentional performance was used. We evaluated whether diabetes mellitus disposes to distinct cognitive dysfunction after coronary artery bypass grafting (CABG). Methods: Three aspects in attentional performance were prospectively tested with three different tests (alertness: composed of un-cued and cued reaction, divided attention, and selective attention) by a computerized tool one day before and seven days after CABG in a highly selected cohort of 30 males, 10 of whom had diabetes. Statistical comparisons were done with analysis of variance for repeated measurements and Fisher´s LSD. Results: Prior to CABG there was no statistically meaningful difference between diabetics and non-diabetics. Postoperatively, diabetic patients performed significantly worse than non-diabetics in tests for un-cued (p=0.01) and cued alertness (p=0.03). Test performance in divided attention was worse after CABG but independent of diabetes status. Selective attention was neither affected by diabetes status nor by CABG itself. Conclusions: Diabetes may have an impact on cognitive performance after CABG. More severe deficits in alertness may point to underlying microvascular disease.},
  subject      = {Medizin},
  language  = {en}
}
@article{ShityakovBroscheitFoerster2013,
  author    = {Shityakov, Sergey and Broscheit, Jens and F{\"o}rster, Carola},
  title     = {Multidrug resistance protein P-gp interaction with nanoparticles (fullerenes and carbon nanotube) to assess their drug delivery potential: a theoretical molecular docking study.},
  series = {International journal of computational biology and drug design},
  volume    = {6},
  journal   = {International journal of computational biology and drug design},
  number    = {4},
  doi       = {10.1504/IJCBDD.2013.056801},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132089},
  pages     = {343-357},
  year      = {2013},
  abstract  = {P-glycoprotein (P-gp)-mediated efflux system plays an important role to maintain chemical balance in mammalian cells for endogenous and exogenous chemical compounds. However, despite the extensive characterisation of P-gp potential interaction with drug-like molecules, the interaction of carbon nanoparticles with this type of protein molecule is poorly understood. Thus, carbon nanoparticles were analysed, such as buckminsterfullerenes (C20, C60, C70), capped armchair single-walled carbon nanotube (SWCNT or C168), and P-gp interactions using different molecular docking techniques, such as gradient optimisation algorithm (ADVina), Lamarckian genetic algorithm (FastDock), and shape-based approach (PatchDock) to estimate the binding affinities between these structures. The theoretical results represented in this work show that fullerenes might be P-gp binders because of low levels of Gibbs free energy of binding (ΔG) and potential of mean force (PMF) values. Furthermore, the SWCNT binding is energetically unfavourable, leading to a total decrease in binding affinity by elevation of the residual area (Ares), which also affects the π-π stacking mechanisms. Further, the obtained data could potentially call experimental studies using carbon nanostructures, such as SWCNT for development of drug delivery vehicles, to administer and assess drug-like chemical compounds to the target cells since organisms probably did not develop molecular sensing elements to detect these types of carbon molecules.},
  language  = {en}
}
@article{ShityakovPuskasRoeweretal.2014,
  author    = {Shityakov, Sergey and Pusk{\´a}s, Istv{\´a}n and Roewer, Norbert and F{\"o}rster, Carola and Broscheit, Jens},
  title     = {Three-dimensional quantitative structure-activity relationship and docking studies in a series of anthocyanin derivatives as cytochrome P450 3A4 inhibitors},
  series = {Advances and Applications in Bioinformatics and Chemistry},
  volume    = {7},
  journal   = {Advances and Applications in Bioinformatics and Chemistry},
  doi       = {10.2147/AABC.S56478},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120226},
  pages     = {11-21},
  year      = {2014},
  abstract  = {The cytochrome P450 (CYP)3A4 enzyme affects the metabolism of most drug-like substances, and its inhibition may influence drug safety. Modulation of CYP3A4 by flavonoids, such as anthocyanins, has been shown to inhibit the mutagenic activity of mammalian cells. Considering the previous investigations addressing CYP3A4 inhibition by these substances, we studied the three-dimensional quantitative structure-activity relationship (3D-QSAR) in a series of anthocyanin derivatives as CYP3A4 inhibitors. For the training dataset (n=12), comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) yielded crossvalidated and non-crossvalidated models with a q (2) of 0.795 (0.687) and r (2) of 0.962 (0.948), respectively. The models were also validated by an external test set of four compounds with r (2) of 0.821 (CoMFA) and r (2) of 0.812 (CoMSIA). The binding affinity modes associated with experimentally derived IC50 (half maximal inhibitory concentration) values were confirmed by molecular docking into the CYP3A4 active site with r (2) of 0.66. The results obtained from this study are useful for a better understanding of the effects of anthocyanin derivatives on inhibition of carcinogen activation and cellular DNA damage.},
  language  = {en}
}
@article{WilhelmsBroscheitShityakov2023,
  author    = {Wilhelms, Benedikt and Broscheit, Jens and Shityakov, Sergey},
  title     = {Chemical analysis and molecular modelling of cyclodextrin-formulated propofol and its sodium salt to improve drug solubility, stability and pharmacokinetics (cytogenotoxicity)},
  series = {Pharmaceuticals},
  volume    = {16},
  journal   = {Pharmaceuticals},
  number    = {5},
  issn      = {1424-8247},
  doi       = {10.3390/ph16050667},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313705},
  year      = {2023},
  abstract  = {Propofol is a widely used general anesthetic in clinical practice, but its use is limited by its water-insoluble nature and associated pharmacokinetic and pharmacodynamic limitations. Therefore, researchers have been searching for alternative formulations to lipid emulsion to address the remaining side effects. In this study, novel formulations for propofol and its sodium salt Na-propofolat were designed and tested using the amphiphilic cyclodextrin (CD) derivative hydroxypropyl-β-cyclodextrin (HPβCD). The study found that spectroscopic and calorimetric measurements suggested complex formation between propofol/Na-propofolate and HPβCD, which was confirmed by the absence of an evaporation peak and different glass transition temperatures. Moreover, the formulated compounds showed no cytotoxicity and genotoxicity compared to the reference. The molecular modeling simulations based on molecular docking predicted a higher affinity for propofol/HPβCD than for Na-propofolate/HPβCD, as the former complex was more stable. This finding was further confirmed by high-performance liquid chromatography. In conclusion, the CD-based formulations of propofol and its sodium salt may be a promising option and a plausible alternative to conventional lipid emulsions.},
  language  = {en}
}