Nucleotide derivatives of 2,7-diaminomitosene.
Treatment of mitomycin C with pyrimidine nucleotides in acidic media produced derivatives of 2,7-diaminomitosene in which C-1 was covalently bound to the phosphate group of the nucleotides. On reduction, these derivatives liberated the nucleotides and a mitomycin intermediate that alkylated DNA. Their reduction in the presence of 2'-deoxyguanosine produced some bifunctional alkylation as did mitomycin C. They were readily taken up by L1210 leukemia cells, in which they showed potent cytotoxicity. These properties suggest that they are acting as prodrugs capable of conversion into two active species. The uridylate derivative showed activity comparable to that of mitomycin C against P-388 leukemia in mice.
Iyengar
B S
BS
Department of Pharmaceutical Sciences and Cancer Center, University of Arizona, Tucson 85721.
Dorr
R T
RT
Remers
W A
WA
Kowal
C D
CD
D000478:Alkylation; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D055598:Chemical Phenomena; D002621:Chemistry; D007939:Leukemia L1210 / Q000188:drug therapy / Q000378:metabolism; D007941:Leukemia P388 / Q000188:drug therapy; D008297:Male; D051379:Mice; D008937:Mitomycins / Q000138:chemical synthesis* / Q000627:therapeutic use*; D009711:Nucleotides / Q000138:chemical synthesis* / Q000627:therapeutic use; D011355:Prodrugs / Q000138:chemical synthesis / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D008937:Mitomycins; D009711:Nucleotides; D011355:Prodrugs; C046001:mitosene; C056707:2,7-diaminomitosene