Designing of multi-targeted molecules using combination of molecular screening and in silico drug cardiotoxicity prediction approaches

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Date

2014

Authors

Buturak, Birce
Durdagi, Serdar
Noskov, Sergei Y.
Ildeniz, A. Tugba Ozal

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Publisher

Elsevier Science Inc

Research Projects

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Abstract

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. (C) 2014 Elsevier Inc. All rights reserved.

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Keywords

Protein database search, Molecular docking, Molecular engineering, Carbonic anhydrase inhibitors, Multi-targeted agents, hERG ion channel

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Citation

5

WoS Q

N/A

Scopus Q

Q2

Source

Volume

50

Issue

Start Page

16

End Page

34