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 Chemjournal_title
European journal of medicinal chemistryauthors
More UA,Joshi SD,Aminabhavi TM,Kulkarni VH,Badiger AM,Lherbet Cdoi
10.1016/j.ejmech.2015.03.013subject
Has Abstractpub_date
2015-04-13 00:00:00pages
317-39eissn
0223-5234issn
1768-3254pii
S0223-5234(15)00180-4journal_volume
94pub_type
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