ml4004815_si_001.pdf (480.91 kB)
Biarylmethoxy Nicotinamides As Novel and Specific Inhibitors of Mycobacterium tuberculosis
journal contribution
posted on 2014-05-08, 00:00 authored 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. TantryA 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.