Mitomycin C analogues with increased metal complexing ability.
Twenty-three new mitomycin C analogues designed to have increased metal complexing ability were synthesized and tested against P388 leukemia in mice. Their ability to complex Cu(II) was revealed by the shifts in their UV absorption spectra caused by this metal. One analogue was clearly more active than mitomycin C in the antitumor assay and two others had good activity. Correlation between antitumor activity and Cu(II) complexing ability was ambiguous. The most active compounds were either not complexers or they were complexers limited to the 2-(2-pyridyl)alkyl type substituent on N7. A variety of amino acid substituents on N7 showed only weak antitumor activity.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D003035:Cobalt / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D007941:Leukemia P388 / Q000188:drug therapy; D008670:Metals / Q000378:metabolism*; D051379:Mice; D016685:Mitomycin; D008937:Mitomycins / Q000138:chemical synthesis / Q000378:metabolism / Q000627:therapeutic use*; D009532:Nickel / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet; D015032:Zinc / Q000378:metabolism
D008670:Metals; D008937:Mitomycins; D003035:Cobalt; D016685:Mitomycin; D003300:Copper; D009532:Nickel; D015032:Zinc