In the search for new anticancer drugs XII. Synthesis and biological evaluation of spin labeled nitrosoureas

• Published in: Life sciences (1973) Vol. 36; no. 15; p. 1479
• Main Authors: Sosnovsky, G, Li, S W
• Format: Journal Article
• Language: English
• Published: Netherlands 15.04.1985
• Subjects: Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - toxicity; Cyclic N-Oxides; Ethylnitrosourea - analogs & derivatives; Lethal Dose 50; Leukemia P388 - drug therapy; Lomustine - therapeutic use; Male; Mice; Nitrosourea Compounds - chemical synthesis; Nitrosourea Compounds - pharmacology; Nitrosourea Compounds - toxicity; Spin Labels - chemical synthesis
• ISSN: 0024-3205
• DOI: 10.1016/0024-3205(85)90056-6

The spin labeled nitrosourea 1-(2-chloroethyl)-3-(1-oxyl-2,2,6,6- tetramethyl-piperidinyl)-1-nitrosourea (SLCNU, 4) and its analogues 5-7 were synthesized either by a regio-selective method or by a conventional route via the nitrosation of the spin labeled intermediates (11a-e). Nitrosation of the ureas 11a-e with dinitrogen tetraoxide resulted in better yields than those obtained with sodium nitrite. The nitrosoureas 4-8 were tested for their anticancer activity against the lymphocytic leukemia P388 in mice. Thus, either at the equal molar dose or at the dose of equal toxicity level, the SLCNU (4) was found to be more active than the clinically used CCNU (1). Unlike CCNU (1) whose LD50 is 56 mg/kg, the SLCNU (4) possesses a low toxicity (LD50 123 mg/kg). Therefore, SLCNU (4) is a promising new entry into the nitrosourea class of anticancer drugs.