Structure-activity comparison of mitomycin C and mitomycin A analogues (review).
Over 600 analogues of mitomycin C (MMC) have been made in the past and more recently a number of Mitomycin A (MMA) derivatives have been prepared. Since many of the MMA type had the same organic side chain at the 7-position as previously prepared MMC analogues it was of interest to see if the biological effects of MMCs could predict for those of MMAs. Using the P388 leukemia model it was possible to compare the activity of 27 matched pairs and the potency of 24 pairs. It was found that antitumor effects did not correlate but that MMAs were significantly more potent than MMCs. These findings were duplicated in tests of 7 pairs against subcutaneously implanted B16 melanoma. We conclude that any MMA derivative would have a high likelihood of being more potent than its MMC equivalent but that its antitumor effects must be independently determined since they cannot be predicted from the results with MMC analogs.
Bradner
W T
WT
Pharmaceutical Research and Development Division, Bristol-Myers Company, Syracuse NY 13221-4755.
Remers
W A
WA
Vyas
D M
DM
D000818:Animals; D004353:Drug Evaluation, Preclinical; D007941:Leukemia P388 / Q000188:drug therapy*; D007942:Leukemia, Experimental; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D016685:Mitomycin; D008937:Mitomycins / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
D008937:Mitomycins; D016685:Mitomycin