M. Kono et al., SYNTHESIS AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF NEW DIMERIC MITOMYCIN DERIVATIVES - 7-N,7'-N'-BIS(OMEGA-THIOALKYL)DIMITOMYCINS, Journal of antibiotics, 46(9), 1993, pp. 1428-1438
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 betw
een 1 and 8, and 1 and cystamine. The observation of the time course f
or the reaction revealed the mechanism of the formation of 7 and 8. Th
e rapid oxidation of cysteamine by the quinone of 1 gave cystamine, wh
ich 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(omega-thioalkyl)dimitomycins were synthesized. They also s
howed remarkable antitumor activities against HeLa-S3 in vitro, sarcom
a 180 (sc-ip), leukemia P388 (ip-ip) in vivo. In these evaluations, co
mpound 7 demonstrated unique potency.