Isolation, synthesis, and antitumor evaluation of spirohydantoin aziridine, a mutagenic metabolite of spirohydantoin mustard.
Spirohydantoin mustard (SHM), a central nervous system directed nitrogen mustard with anticancer activity, was metabolized in the presence of mouse liver postmitochondrial supernatant (9000g fraction) to a nonpolar alkylating metabolite. The metabolite was isolated by thin-layer chromatography of chloroform or ethyl acetate extracts of incubation mixtures, and its structure was established by mass spectral analysis, synthesis, and cochromatography. The metabolite, spirohydantoin aziridine, was mutagenic for Salmonella typhimurium TA1535 in the Ames assay but inactive as an antitumor agent against P388 leukemia in vivo.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D001388:Aziridines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D001389:Azirines / Q000138:chemical synthesis*; D001711:Biotransformation; D004353:Drug Evaluation, Preclinical; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens / Q000138:chemical synthesis*; D009154:Mutation; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001388:Aziridines; D001389:Azirines; D009153:Mutagens; C050497:spirohydantoin aziridine