Design, synthesis, and evaluation of substituted nicotinamide adenine dinucleotide (NAD⁺) synthetase inhibitors as potential antitubercular agents.

ABSTRACT: Nicotinamide adenine dinucleotide (NAD⁺) synthetase catalyzes the last step in NAD⁺ biosynthesis. Depletion of NAD⁺ is bactericidal for both active and dormant Mycobacterium tuberculosis (Mtb). By inhibiting NAD⁺ synthetase (NadE) from Mtb, we expect to eliminate NAD⁺ production which will result in cell death in both growing and nonreplicating Mtb. NadE inhibitors have been investigated against various pathogens, but few have been tested against Mtb. Here, we report on the expansion of a series of urea-sulfonamides, previously reported by Brouillette et al. Guided by docking studies, substituents on a terminal phenyl ring were varied to understand the structure-activity-relationships of substituents on this position. Compounds were te

SUBMITTER: Wang X 

PROVIDER: S-EPMC6190683 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature