ABSTRACT
A new naturally occurring mitomycin, 10-decarbamoyloxy-9-dehydromitomycin B (1), was prepared by treating mitomycin B with sodium hydride. Its analogs having an exo-cyclic double bond in their structure were also synthesized. These compounds showed antibacterial and cytotoxic activities. Among them, 7-amino-10-decarbamoyloxy-9-dehydro-7-demethoxymitomycin B (2) was the most potent growth inhibitor of KB cells in vitro and, accordingly, it appears to be a potential antitumor agent.
Subject(s)
Antibiotics, Antineoplastic/pharmacology , Indolequinones , Mitomycins/pharmacology , Antibiotics, Antineoplastic/chemical synthesis , Bacteria/drug effects , Mitomycins/chemical synthesis , Structure-Activity RelationshipABSTRACT
A facile alcoholysis of 7-methoxymitosanes and 5-methoxyindolequinone under basic conditions was discovered and a series of 7-alkoxymitosanes were synthesized from mitomycins A and B using this reaction. They showed strong antibacterial activity against various Gram-positive and Gram-negative bacteria and were potent inhibitors of cultivating HeLa S-3 cells in vitro. Among them, 7-n-propoxy-7-demethoxymitomycin A (2) showed the strongest antitumor activity against solid type Sarcoma-180 in mice.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Mitomycins/analogs & derivatives , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/toxicity , Bacteria/drug effects , Chemical Phenomena , Chemistry , Lethal Dose 50 , Magnetic Resonance Spectroscopy , Mice , Mitomycins/chemical synthesis , Mitomycins/pharmacology , Mitomycins/toxicity , Structure-Activity RelationshipABSTRACT
The antitumor activity of 7-N-phenyl derivatives of mitomycin C was tested in an ip-ip system of mouse leukemia P388 by single administration. The compounds tested were 7-N-phenyl-, 7-N-(p-aminophenyl)-, 7-N-(p-hydroxyphenyl)- and 7-N-(p-chlorophenyl)-mitomycin C. The maximum increases in life span (ILSmax) obtained were 124, 169, > 386 and 112%, respectively, that with mitomycin C being 104%. 7-N-(p-Hydroxyphenyl)-mitomycin C showed a higher ILS% than its ortho and meta isomers. Thus, 7-N-(p-hydroxyphenyl)-mitomycin C was the most effective of these compounds.
