Design and synthesis of substrate-mimic inhibitors of mycothiol-S-conjugate amidase from Mycobacterium tuberculosis

The Staudinger reaction between a polymer-supported triphenylphosphine reagent and pseudo-disaccharide azides is successfully applied to synthesize a variety of substrate-mimic mycothiol analogs. Screening of this new group of analogs against the mycobacterial detoxification enzyme mycothiol-S-conjugate amidase (MCA) yielded several modest inhibitors (IC50 values around 50 μM) and provided additional structure–activity relationships for future optimization of inhibitors of MCA and its homologs.