Antitumor action of N-(2-chloroethyl)-N-nitrosocarbamoyl derivatives of biologically active polypeptide hormone fragments.
The antitumor action of the 2-chloroethylnitrosocarbamoyl derivatives of peptides related to the 9-13 amino acid residues of alpha-MSH/ACTH and of the C-terminal tetrapeptide analogue of gastrin have been investigated. Series of 2-chloroethylnitrosoureas attached to amino acids, di-, tri-, tetra-, or pentapeptides were examined in a primary screening system. Among these compounds the Pro-Val-, Lys-Pro-Val-, and Trp-Gly-Lys-Pro-Val-containing 2-chloroethylnitrosocarbamoyl groups were the most effective in the L1210 system. The human melanoma xenograft line was also affected by these agents, while colorectal xenografts were insensitive. A combination of tripeptide-2-chloroethyl-nitrosourea with BCNU induced more than additive growth inhibition of L1210 leukemia.
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002330:Carmustine / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D005260:Female; D007274:Injections, Intraperitoneal; D007939:Leukemia L1210 / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D009607:Nitrosourea Compounds / Q000627:therapeutic use*; D010455:Peptides
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D010455:Peptides; D002330:Carmustine