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

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

Liyanarachchi, A.J.; Valentin, G.; Andreana, P.R. Synthesis and inhibition studies of substrate analogues for MshC (cysteine ligase) enzyme in Mycobacterium tuberculosis. Carbohydrate Research 2025, 558, 109652. https://doi.org/10.1016/j.carres.2025.109652

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Abstract

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 IC₅₀ 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.