Molecular Modeling Studies on 2,4-Disubstituted Imidazopyridines as Anti-Malarials: Atom-Based 3D-QSAR, Molecular Docking, Virtual Screening, In-Silico ADMET and Theoretical Analysis
| Autor: | Suraj N. Mali, Anima Pandey |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
Quantitative structure–activity relationship Virtual screening Anti malarial Molecular model 010405 organic chemistry Chemistry In silico Computational biology 01 natural sciences 0104 chemical sciences Computer Science Applications 03 medical and health sciences Computational Theory and Mathematics Antimalarial Agent Physical and Theoretical Chemistry 030304 developmental biology Malarial parasites |
| Zdroj: | Journal of Computational Biophysics and Chemistry. 20:267-282 |
| ISSN: | 2737-4173 2737-4165 |
| Popis: | Malarial parasites have been reported for moderate-high resistance towards classical antimalarial agents and henceforth development of newer novel chemical entities targeting multiple targets rather than targeting single target will be a highly promising strategy in antimalarial drug discovery. Herein, we carried out molecular modeling studies on 2,4-disubstituted imidazopyridines as anti-hemozoin formation inhibitors by using Schrödinger’s molecular modeling package (2020_4). We have developed statistically robust atom-based 3D-QSAR model (training set, [Formula: see text]; test set, [Formula: see text]; [Formula: see text] [Formula: see text]; root-mean-square error, [Formula: see text]; standard deviation, [Formula: see text]). Our molecular docking, in-silico ADMET analysis showed that dataset molecule 37, has highly promising results. Our ligand-based virtual screening resulted in top five ZINC hits, among them ZINC73737443 hit was observed with lesser energy gap, i.e. 7.85[Formula: see text]eV, higher softness value (0.127[Formula: see text]eV), and comparatively good docking score of [Formula: see text]10.2[Formula: see text]kcal/mol. Our in-silico analysis for a proposed hit, ZINC73737443 showed that this molecule has good ADMET, in-silico nonames toxic as well as noncarcinogenic profile. We believe that further experimental as well as the in-vitro investigation will throw more lights on the identification of ZINC73737443 as a potential antimalarial agent. |
| Databáze: | OpenAIRE |
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