Abstract
As we are aware of the alarming rate of the tuberculosis multi drug resistant and extensive drug resistance, it necessitates for a novel drug target. In this investigation, we performed pharmacophore assisted virtual screening on analogs of 2-methyl heptyl isonicotinate against GlmU enzyme of Mycobacterium tuberculosis. Recent reports suggested the GlmU enzyme as a key protein in UDPGlcNAc biosynthesis. Inhibition of the enzyme often results in cell lysis and cell death, and hence GlmU is a potential drug target. Besides, 2-methylheptyl isonicotinate has a strong antibacterial activity against Mycobacterium tuberculosis. In the present investigation, pharmacophore modeling was performed for GlmU enzyme and molecular docking was carried out at the predicted site. The molecular docking simulation results revealed the analogs exhibiting favourable docking score inhibiting the enzyme. The analogs used in the present investigation are 90% similar with 2- methyl heptyl isonicotinate. Hence the analogs could also possess strong anti bacterial property against Mycobacterium tuberculosis. Additionally, the ADME-Toxicity parameters for the top docking hits showed two analogs viz CID55259454, CID4147645, CID20033037 and CID531736 possessed enhanced pharmacological parameters than market approved drug isoniazid. And hence these candidates may serve as a novel inhibitor against Mtb GlmU enzyme.
Keywords: ADME-Toxicity, GlmU, molecular docking, pharmacophore.
Graphical Abstract
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