ChemInform Abstract: Thienopyrimidines as Novel Inhibitors of Mycobacterium tuberculosis: Synthesis and in vitro Studies.

Abstract

Thienopyrimidines as Novel Inhibitors of Mycobacterium tuberculosis: Synthesis and in vitro Studies. -The compounds (X) are tested for growth inhibition of Mycobacterium tuberculosis H37Rv. The compounds (Xb)-(Xg) exhibit good antimycobacterial activity. They are also subject for cytotoxicity studies and possess poor cytotoxicity. -(RASHMI*, P.; NARGUND, L. V. G.; HAZRA, K.; CHANDRA, J. N. N. S.; Arch. Pharm. (Weinheim, Ger.) 344 (2011) 7, 459-465, http://dx.

Rv2466c Mediates the Activation of TP053 To Kill Replicating and Non-replicating Mycobacterium tuberculosis

“…In that context, the search for alternative drug therapies to combat TB has led to our interest in the thienopyrimidine (TP) scaffold. − A new series of TP derivatives was carefully synthesized and tested for anti-TB activity, with the most potent inhibitor TP053 displaying very low MIC values of 0.125 and 0.800 μg/mL in replicating and non-replicating models, respectively. Using a combination of chemical synthesis, isolation of M. tuberculosis resistant mutants, genetic validation, and biochemical and crystallographic studies we provide evidence indicating that TP053 is a prodrug activated by a novel thioredoxin-like protein (Rv2466c) in a redox dependent manner.…”