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System for Efficacy and Cytotoxicity Screening of Inhibitors Targeting Intracellular Mycobacterium tuberculosis
Published on: April 5, 2017
Discovery of target based novel pyrrolyl phenoxy derivatives as antimycobacterial agents: an in silico approach
Uttam A More1, Shrinivas D Joshi2, Tejraj M Aminabhavi2
1Novel Drug Design and Discovery Laboratory, Department of Pharmaceutical Chemistry, S.E.T's College of Pharmacy, Sangolli Rayanna Nagar, Dharwad 580 002, India; Centre for Research and Development, Prist University, Thanjavur, Tamil Nadu 613 403, India.
Abstract:
A new series of pyrrolyl phenoxy derivatives bearing alkoxy linker were synthesized and evaluated for anti-tubercular activity (anti-TB) against Mycobacterium tuberculosis. Molecular modeling, pharmacophore constructed using GALAHAD to produce an effective alignment of data set and evaluated by Pareto ranking. The pharmacophore features were filtered by Surflex-dock study using enoyl ACP reductase from M. tuberculosis, which is one of the key enzymes involved in type II fatty acid biosynthesis pathway of M. tuberculosis. Compound 6a27 showed the H-bond with NAD(+), whereas compound 6a26 showed H-bonds with Tyr158, Thr196, Met199 and NAD(+) that fitted well into the binding pocket of target InhA. The alkoxy linker bridge and acceptor groups with benzene ring were advantageous for anti-TB activity, which merit further investigation.
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