Reductive activation of mitomycin A by thiols.
[reaction: see text]. Mitomycin C is unchanged upon exposure to thiols under physiological conditions. Its more toxic variant, mitomycin A (MA), undergoes elimination of methanol to give a variety of mitosene derivatives, diagnostic of its activation to a reactive electrophile. Evidence is presented for a novel reductive mechanism, characterized by the transient addition of a thiol to the quinone of MA, followed by intramolecular electron transfer, leading to reduced quinone and oxidized thiol.
Paz
M M
MM
Department of Chemistry, Hunter College, City University of New York, New York, New York 10021, USA.
Tomasz
M
M
D000432:Methanol / Q000737:chemistry; D008937:Mitomycins / Q000737:chemistry* / Q000494:pharmacology; D010084:Oxidation-Reduction; D013438:Sulfhydryl Compounds / Q000737:chemistry*
D008937:Mitomycins; D013438:Sulfhydryl Compounds; C046000:mitomycin A; D000432:Methanol