title: Mechanistic investigation of the oxidation of hydrazides: implications for the activation of the TB drug isoniazid.
abstract: Aryl hydrazides are oxidised to acyl radicals through a mechanism involving diimide intermediates that are prone to nucleophilic acyl substitution. This oxidation occurs regardless of the oxidant involved, however there is no evidence that the acyl radical formed undergoes further oxidation to the corresponding acylium ion, even in the presence of strong oxidants. This study may provide insight into the mechanism of isoniazid resistance in Mycobacterium tuberculosis.
authors.affiliation: School of Chemistry, University of Tasmania, Hobart, Australia.
authors.forename: Ruth I J
authors.initials: RI
authors.lastname: Amos
authors.forename: Brendon S
authors.initials: BS
authors.lastname: Gourlay
authors.forename: Brian F
authors.initials: BF
authors.lastname: Yates
authors.forename: Carl H
authors.initials: CH
authors.lastname: Schiesser
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Lewis
authors.forename: Jason A
authors.initials: JA
authors.lastname: Smith
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007538:Isoniazid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D010084:Oxidation-Reduction; D011789:Quantum Theory; D013329:Structure-Activity Relationship
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid