M. Colvin, R. Brundrett, W. Cowens
Mar 15, 1976
Citations
1
Influential Citations
97
Citations
Quality indicators
Journal
Biochemical pharmacology
Abstract
Abstract A comparison of the aqueous decomposition products of several haloethylnitrosoureas has led to a suggested mode of decomposition and antitumor effect for these compounds. 1,3-Bis-chloroethyl-1-nitrosourea (BCNU), 1-chloroethyl-3-cyclohexyl-1-nitrosourea (CCNU), 1,3-bis-fluoroethyl-1-nitro-sourea (BFNU) and 1-chloroethyl-1-nitrosourea (CNU) decompose in buffered aqueous solution to yield haloethanol, vinyl halide, dihaloethane and acetaldehyde. Evidence is presented that these products are derived from an intermediate haloethyl carbonium ion. On the other hand, 1-chloroethyl-3,3-dimethyl-1-nitrosourea decomposes slowly in aqueous solution, generates acetaldehyde, but not the other volatile compounds described above, and is not toxic to murine L1210 leukemia cells in vitro . In contrast to the disubstituted nitrosoureas, chloroethylnitrosourea does not generate an organic isocyanate on aqueous decomposition, but is a very active antitumor agent both in vitro and in vitro . These observations support the hypothesis that the antitumor activity of the chloroethylnitrosoureas is due to the facile decomposition of the parent molecule to form a chloroethyl carbonium ion (or diazonium precursor).