In vitro cytotoxicity and differential cellular sensitivity of new N-methyl and N-propargyl urea and nitrosourea derivatives of diamino acids against sixty human NCI tumor cell lines.
The in vitro cytotoxicity and differential cellular sensitivity of a series of new N-methyl and N-propargyl urea and nitrosourea derivatives of diamino acids were determined in the National Cancer Institute's primary antitumor drug screen. These compounds have a level of cytotoxic activity comparable to BCNU, CCNU and Methyl-CCNU. In this series of diamino acid derivatives, the N-nitroso group does not seems to be essential to the in vitro activity of these compounds. The N-Propargyl derivatives have shown significantly more differential cellular sensitivity than the N-Methyl derivatives. Hence, the N-Propargyl group seems to induce more cell line specificity in our compounds. Based on their in vitro cytotoxic activity and mostly their pattern of differential cellular sensitivity, two compounds described in this work have been selected by the NCI for further development. These compounds are currently being screened in animal models.
Gallant
G
G
Medicinal Chemistry Laboratory, Faculty of Pharmacy, University of Montréal, Québec, Canada.
Salvador
R
R
Dulude
H
H
D000970:Antineoplastic Agents / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D014508:Urea