Synthesis of mycothiol conjugate analogues and evaluation of their antimycobacterial activity.

Drug-resistant Mycobacterium tuberculosis is a growing health problem. As proof of principle that the bacterial-specific metabolite mycothiol could be used as a delivery agent for antimycobacterial agents, simplified analogues of mycothiol were synthesised containing an S-trichloroethenyl substituted cysteine residue. It was envisaged that uptake of the mycothiol analogue would be followed by release of the known cytotoxin S-trichloroethenyl cysteine by the action of mycothiol S-conjugate amidase or its paralog, mycothiol deacetylase MshB.