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

•Multiple screening of 229 proteins showed a few targets for potency of multi-functional drugs.•These drugs are tested in silico for their cardiotoxicity risks.•Derived results can be used to improve the desired effects of these compounds by molecular engineering studies.

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.

Graphical abstractIn this study, multi-target interactions and multi-functional potentials of a set of phenol- and indole-based carbonic anhydrase inhibitors are investigated. For this aim, molecular interactions of 26 ligands into binding sites of 229 proteins from different classes were screened to determine potential concurrent interactions of these ligands with potential impacts for drug applications. Results showed potency of multi-targeted drugs of a few compounds from investigated ligand set. These ligands are also tested in silico for their cardiotoxicity risks.Figure optionsDownload full-size imageDownload high-quality image (228 K)Download as PowerPoint slide