Preparation and antitumor activity of new mitomycin A analogues.
A series of 26 mitomycin A analogues including 23 new ones was prepared by a variety of methods. The most useful methods were alkoxide exchange on mitomycin A and treatment of 7-hydroxymitosane with 3-substituted 1-phenyltriazenes. Many of the new analogues were superior to mitomycin C in the P388 leukemia assay and the more stringent subcutaneous B16 melanoma assay both in mice. Four of them gave long-term survivors in the latter assay. Quantitative correlations between log P and antitumor activity were not possible, but some guidelines for future analogue development are proposed.
D000818:Animals; D004353:Drug Evaluation, Preclinical; D007202:Indicators and Reagents; D007941:Leukemia P388 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008937:Mitomycins / Q000138:chemical synthesis* / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
D007202:Indicators and Reagents; D008937:Mitomycins; C046000:mitomycin A