Designing of multi-targeted molecules using combination of molecular screening and in silico drug cardiotoxicity prediction approaches.
We have previously investigated and reported a set of phenol- and indole-based derivatives at the binding pockets of carbonic anhydrase isoenzymes using in silico and in vitro analyses. In this study, we extended our analysis to explore multi-targeted molecules from this set of compounds. Thus, 26 ligands are screened at the binding sites of 229 proteins from 5 main enzyme family classes using molecular docking algorithms. Derived docking scores are compared with reported results of ligands at carbonic anhydrase I and II isoenzymes. Results showed potency of multi-targeted drugs of a few compounds from investigated ligand set. These promising ligands are then tested in silico for their cardiotoxicity risks. Results of this work can be used to improve the desired effects of these compounds by molecular engineering studies. In addition these results may lead to further investigation of studied molecules by medicinal chemists to explore different therapeutic aims.
Computational Biology and Bioinformatics, Graduate School of Science and Engineering, Kadir Has University, Istanbul, Turkey.
Birce
B
Buturak
Department of Biophysics, School of Medicine, Bahcesehir University, Istanbul, Turkey.
Serdar
S
Durdagi
Institute for Biocomplexity and Informatics, University of Calgary, Calgary, AB, Canada. Electronic address: snoskov@ucalgary.ca.
Sergei Y
SY
Noskov
Computational Biology and Bioinformatics, Graduate School of Science and Engineering, Kadir Has University, Istanbul, Turkey; Department of Bioinformatics and Genetics, Kadir Has University, Istanbul, Turkey. Electronic address: tugba.ozal@khas.edu.tr.
A Tugba Ozal
AT
Ildeniz
D001665:Binding Sites; D002256:Carbonic Anhydrases / Q000737:chemistry / Q000378:metabolism; D066126:Cardiotoxicity; D003198:Computer Simulation; D030562:Databases, Protein; D015195:Drug Design; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
D007527:Isoenzymes; D008024:Ligands; D011506:Proteins; D002256:Carbonic Anhydrases
Carbonic anhydrase inhibitors; Molecular docking; Molecular engineering; Multi-targeted agents; Protein database search; hERG ion channel