Synthesis , Quantum mechanical calculation and in silico screening of novel hydrazone derivatives as Mycobacterium tuberculosis enoyl reductase inhibitors

Abstract

A series of novel benzo hydrazide derivatives were synthesized and benzoylated. The compounds were purified and characterized by IR, NMR, Mass spectral studies. Drug likeliness assessment conferred all compounds obeying rule of thumb. Binding energy calculation revealed compounds having electron donating groups having high HOMO values (BS9, BS10, SB9, SB10). Structure based drug design was performed for 48 structures having various heterocyclic moieties, INH, and 10 compounds which are reported in literature as active Inh A inhibitors. Docking and scoring study unravels that our compounds were having 1-5 H-bonding interactions with Tyr158, Ile95, Ile194, Pro 193 H 2 O 856, 502, 563, and 552. Hydrophobic interactions of compounds were found to be with Ala157, Gly96, Ile215, Leu218, Met103, Tyr158, Phe97, Pro156, Ser123 and Iys165. All the compounds have good docking score compared to INH. In vitro anti oxidant activity by nitric oxide scavenging assay was also performed and the results inferred compounds having good docking score are having good activity. The compounds having electron donating groups are having good activity.