title: Synthesis of mycothiol conjugate analogues and evaluation of their antimycobacterial activity.
abstract: 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. Promising activity was displayed against model Mycobacteria, although further development will be required to improve selectivity.
authors.affiliation: Centre for Biodiscovery, Victoria University of Wellington, Wellington 6012, New Zealand.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Riordan
authors.affiliation: Centre for Biodiscovery, Victoria University of Wellington, Wellington 6012, New Zealand.
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Field
authors.affiliation: Centre for Biodiscovery, Victoria University of Wellington, Wellington 6012, New Zealand.
authors.forename: Hilary M
authors.initials: HM
authors.lastname: Corkran
authors.affiliation: Centre for Biodiscovery, Victoria University of Wellington, Wellington 6012, New Zealand.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Dasyam
authors.affiliation: Centre for Biodiscovery, Victoria University of Wellington, Wellington 6012, New Zealand.
authors.forename: Bridget L
authors.initials: BL
authors.lastname: Stocker
authors.affiliation: Centre for Biodiscovery, Victoria University of Wellington, Wellington 6012, New Zealand.
authors.forename: Mattie S M
authors.initials: MS
authors.lastname: Timmer
authors.affiliation: Centre for Biodiscovery, Victoria University of Wellington, Wellington 6012, New Zealand.
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Harvey
authors.affiliation: Centre for Biodiscovery, Victoria University of Wellington, Wellington 6012, New Zealand. Electronic address: paul.teesdale-spittle@vuw.ac.nz.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Teesdale-Spittle
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D003545:Cysteine / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006020:Glycopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007294:Inositol / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects
chemical_list: D000995:Antitubercular Agents; D006020:Glycopeptides; C089265:mycothiol; D007294:Inositol; D003545:Cysteine
keywords: Antibacterial; Antimycobacterial; Mycothiol; Prodrug; Trichlorovinyl cysteine