Synthesis and structure-activity relationships of new dimeric mitomycin derivatives; 7-N,7'-N'-bis(ω-thioalkyl)dimitomycins

Article abstract of DOI:10.7164/antibiotics.46.1428

The reaction between mitomycin A (1) and cysteamine afforded 7-N,7'-N'-bis(2-thioethyl)dimitomycin C (7), 7-N-[2-[(2-aminoethyl)dithio]ethyl]mitomycin C (8), and 7-methoxy mitosenes (10,11). The structures of 7 and 8 were elucidated on the basis of spectroscopy and reactions between 1 and 8, and 1 and cystamine. The observation of the time course for the reaction revealed the mechanism of the formation of 7 and 8. The rapid oxidation of cysteamine by the quinone Or 1 gave cystamine, which was trapped by 1 to give 8, and 8 was additionally reacted with 1 to give 7. Since 7 showed significant antitumor activities, related 7-N,7'-N'-bis(ω-thioalkyl)-dimitomycins were synthesized. They also showed remarkable antitumor activities against HcLa-S₃ in vitro, sarcoma 180 (sc-ip), leukemia P388 (ip-ip) in vivo. In these evaluations, compound 7 demonstrated unique potency.