Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A useful method was found for the conversion of mitomycin C into N-methylmitomycin A. The latter compound gave only two products on acid hydrolysis, the cis- and trans-1-hydroxy-7-methoxy-2-methylaminomitosenes. This selectivity allowed the cis--trans ratio to be quantitatively determined as 4:1. Such a predominance of the cis isomer is unexpected in view of the trans stereochemistry obtained in the opening of simple aziridines. In order to determine if the 9a-methoxy group of mitomycins controlled the direction of aziridine ring opening 7-methoxy-1,2-(N-methylaziridino)mitosene, which lacks this substituent, was prepared and hydrolyzed in acid. It gave the same two products in a 3:1 cis-trans ratio. In the induction of lambda-bacteriophage in Escherichia coli cis-1-hydroxy-7-methoxy-2-methylaminomitosene was more active than the corresponding trans isomer, but both of these compounds were less active than the aziridinomitosene or the mitomycins. Mitomycin A, mitomycin C, and N-methylmitomycin A were active against P388 leukemia in mice.
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PMID:Comparative stereochemistry in the aziridine ring openings of N-methylmitomycin A and 7-methoxy-1,2-(N-methylaziridino)mitosene. 87 53

Over 600 analogues of mitomycin C (MMC) have been made in the past and more recently a number of Mitomycin A (MMA) derivatives have been prepared. Since many of the MMA type had the same organic side chain at the 7-position as previously prepared MMC analogues it was of interest to see if the biological effects of MMCs could predict for those of MMAs. Using the P388 leukemia model it was possible to compare the activity of 27 matched pairs and the potency of 24 pairs. It was found that antitumor effects did not correlate but that MMAs were significantly more potent than MMCs. These findings were duplicated in tests of 7 pairs against subcutaneously implanted B16 melanoma. We conclude that any MMA derivative would have a high likelihood of being more potent than its MMC equivalent but that its antitumor effects must be independently determined since they cannot be predicted from the results with MMC analogs.
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PMID:Structure-activity comparison of mitomycin C and mitomycin A analogues (review). 251 May 80

New mitomycin C and porfiromycin analogues were prepared by treating mitomycin A and N-methylmitomycin A with a variety of amines, including aziridines, allylamines, propargylamines, chloroalkylamines, hydroxyalkylamines, glycine derivatives, aralkylamines, and heterocyclic amines. All analogues were evaluated against P-388 murine leukemia and selected ones were examined for their leukopenic properties. Certain analogues were found to be superior to mitomycin C in potency, efficacy, and therapeutic ratio in the P-388 assay. The most active substituents at the mitosane 7 position included aziridine, 2-methylaziridine, propargylamine, furfurylamine, methyl glycinate, and 3-aminopyridine. Mitomycin A and the 7-aziridino, 7-(2-methylaziridino), and 3-aminopyridine analogues were less leukopenic than mitomycin C. Certain other analogues, including propargylamino and methyl glycinate, were highly leukopenic. The three compounds tested against B-16 melanoma in mice were significantly more effective than mitomycin C in this assay. Previously established structure--activity relationships were found inadequate to account for all of the new data.
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PMID:Development of new mitomycin C and porfiromycin analogues. 732 99