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Biarylmethoxy Nicotinamides As Novel and Specific Inhibitors of Mycobacterium tuberculosis

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journal contribution
posted on 08.05.2014 by Chaitanya Kumar Kedari, Nilanjana Roy Choudhury, Sreevalli Sharma, Parvinder Kaur, Supreeth Guptha, Manoranjan Panda, Kakoli Mukerjee, Vasanthi Ramachandran, Balachandra Bandodkar, Sreekanth Ramachandran, Subramanyam J. Tantry
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 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.

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