Synthesis and preliminary in vitro cytotoxicity evaluation of 1,3-bis-(2-propynyl)-1-nitrosourea (BPNU) and derivatives.
The in vitro cytotoxicity and differential cellular sensitivity of a series of new N1-(propargyl) nitrosourea derivatives, including 1,3-bis-(2-propynyl)-1-nitrosourea (BPNU), a carmustine (BCNU) analog, were determined in the National Cancer Institute's primary antitumor drug screen. BPNU has a level of cytotoxic activity comparable to BCNU, CCNU and Methyl-CCNU. Unexpectedly, the bi-substitution of BPNU at the amino N3 position produced an inactive compound. Compared to BCNU, BPNU has a marked specificity towards leukemic cells and could potentially be useful as an anti-leukemic agent. In this series, the N1-(propargyl) group seems to induce cell line specificity.
Gallant
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G
Medicinal Chemistry Laboratory, Faculty of Pharmacy, University of Montréal, Québec, Canada.
Salvador
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R
Dulude
H
H
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000633:toxicity*; D002289:Carcinoma, Non-Small-Cell Lung; D018288:Carcinoma, Small Cell; D002330:Carmustine / Q000633:toxicity; D002460:Cell Line; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006207:Half-Life; D006801:Humans; D007202:Indicators and Reagents; D007680:Kidney Neoplasms; D007938:Leukemia; D008175:Lung Neoplasms; D008545:Melanoma; D015394:Molecular Structure; D009316:National Institutes of Health (U.S.); D009607:Nitrosourea Compounds / Q000138:chemical synthesis* / Q000633:toxicity*; D010051:Ovarian Neoplasms; D014407:Tumor Cells, Cultured; D014481:United States
D000970:Antineoplastic Agents; D007202:Indicators and Reagents; C092290:NSC 634775; D009607:Nitrosourea Compounds; D002330:Carmustine