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Biarylmethoxy Nicotinamides As Novel and Specific Inhibitors of Mycobacterium tuberculosis.

ABSTRACT: A whole cell based screening effort on a focused library from corporate collection resulted in the identification of biarylmethoxy nicotinamides as novel inhibitors of M. tuberculosis (Mtu) H37Rv. The series exhibited tangible structure-activity relationships, and during hit to lead exploration, a cellular potency of 100 nM was achieved, which is an improvement of >200-fold from the starting point. The series is very specific to Mtu and noncytotoxic up to 250 ?M as measured in the mammalian cell line THP-1 based cytotoxicity assay. This compound class retains its potency on several drug sensitive and single drug resistant clinical isolates, which indicate that the compounds could be acting through a novel mode of action.

SUBMITTER: Kedari CK

PROVIDER: S-EPMC4027638 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Biarylmethoxy Nicotinamides As Novel and Specific Inhibitors of Mycobacterium tuberculosis.

Kedari Chaitanya Kumar CK Roy Choudhury Nilanjana N Sharma Sreevalli S Kaur Parvinder P Guptha Supreeth S Panda Manoranjan M Mukerjee Kakoli K Ramachandran Vasanthi V Bandodkar Balachandra B Ramachandran Sreekanth S Tantry Subramanyam J SJ

ACS medicinal chemistry letters 20140310 5

A whole cell based screening effort on a focused library from corporate collection resulted in the identification of biarylmethoxy nicotinamides as novel inhibitors of M. tuberculosis (Mtu) H37Rv. The series exhibited tangible structure-activity relationships, and during hit to lead exploration, a cellular potency of 100 nM was achieved, which is an improvement of >200-fold from the starting point. The series is very specific to Mtu and noncytotoxic up to 250 μM as measured in the mammalian cell ...[more]

PMID: 24900867

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