New mitomycin analogs produced by directed biosynthesis.
When the normal fermentation medium for the production of mitomycin C with Streptomyces caespitosus is supplemented with a number of primary amines, two new types of mitomycin analogs described as Type I and Type II are produced. Type I analogs are related to mitomycin C with the amine substitution at position C7 on the mitosane ring. Type II analogs also contain the same substitutions at C7 but the conformation of the mitosane ring is related to mitomycin B having an OH at positions C9a and a methyl substituted aziridine. The products obtained from the supplementation of the medium with methylamine, ethylamine, propylamine, propargylamine and 2-methylallylamine were isolated and characterized. In all cases the Type I analogs are more active in a prophage induction test and against L1210 lymphatic leukemia in mice. A number of other amines have been tested and shown to yield new products that have not yet been isolated. No secondary amines are incorporated.
Claridge
C A
CA
Bush
J A
JA
Doyle
T W
TW
Nettleton
D E
DE
Moseley
J E
JE
Kimball
D
D
Kammer
M F
MF
Veitch
J
J
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D007274:Injections, Intraperitoneal; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D008811:Mice, Inbred DBA; D008937:Mitomycins / Q000096:biosynthesis* / Q000627:therapeutic use; D011160:Porfiromycin / Q000096:biosynthesis / Q000627:therapeutic use; D013237:Stereoisomerism
D008937:Mitomycins; C046000:mitomycin A; D011160:Porfiromycin