Synthesis and inhibition studies of substrate analogues for MshC (cysteine ligase) enzyme in Mycobacterium tuberculosis

Mycothiol cysteine ligase (MshC) from Mycobacterium tuberculosis (TB) plays a vital role in the biosynthesis of mycothiol (MSH) and can serve as a potential target for designing novel anti-mycobacterial compounds. Herein we report the synthesis of MshC substrate GlcN-Ins and substrate-based analogues as potential inhibitors for MshC. We obtained IC 50 values in the micromolar range for our substrate analogues; comparable to other reported inhibitors. Our strategy exploits the synthesis of substrate analogues through the modification of the C-2 position of GlcN-Ins.