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Designing of multi-targeted molecules using combination of molecular screening and in silico drug cardiotoxicity prediction approaches |
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| Affiliation: | 1. School of BioSciences, The University of Melbourne, BioSciences 1, Tin Alley, Parkville, VIC 3010, Australia;2. Atomic Medicine Initiative, Faculty of Science, University of Technology Sydney, PO Box 123, 15 Broadway, Ultimo, NSW 2007, Australia;3. Institute for Biomedical Materials and Devices, Faculty of Science, University of Technology Sydney, PO Box 123, 15 Broadway, Ultimo, NSW 2007, Australia;1. Mehmet Akif Ersoy University, Burdur, Turkey;2. Mehmet Akif Ersoy University, Zeliha Tolunay Applied Technology and Business School, Burdur, Turkey;3. Süleyman Demirel University, Department of Computer Engineering, Isparta, Turkey\n |
| 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. |
| Keywords: | Protein database search Molecular docking Molecular engineering Carbonic anhydrase inhibitors Multi-targeted agents hERG ion channel |
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