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

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.