Discovery of target based novel pyrrolyl phenoxy derivatives as antimycobacterial agents: an in silico approach.

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.

journal_name

Eur J Med Chem

authors

More UA,Joshi SD,Aminabhavi TM,Kulkarni VH,Badiger AM,Lherbet C

doi

10.1016/j.ejmech.2015.03.013

subject

Has Abstract

pub_date

2015-04-13 00:00:00

pages

317-39

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(15)00180-4

journal_volume

94

pub_type

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