Alkylarylnitrosoureas--stability in aqueous solution, partition coefficient, alkylating activity and its relationship to SCE induction in Chinese hamster V 79-E cells.
The alkylating activity, chemical stability in aqueous solution (pH 7.0; 37 degrees C), and partition coefficient (octanol/water) of the following compounds were determined: 1-methyl-3-phenyl-1-nitrosourea (MPNU), 1-ethyl-3-phenyl-1-nitrosourea (EPNU), 1-isopropyl-3-phenyl-1-nitrosourea (i-PrPNU), 1-methyl-3-(p-fluorophenyl)-1-nitrosourea (F-MPNU), 1-methyl-3-(p-chlorophenyl)-1-nitrosourea (Cl-MPNU), 1-methyl-3-(p-bromophenyl)-1-nitrosourea (Br-MPNU), 1,3-dimethyl-3-phenyl-1-nitrosourea (DMPNU), and 1-methyl-3-naphthyl-1-nitrosocarbamate (NCA). 1-Methyl-1-nitrosourea (MNU) and 1-ethyl-1-nitrosourea (ENU) were used for the comparison. THe rate of decomposition in aqueous solution is discussed concerning the influences of the substituents at the 1- and 3-N-atom. The mono- and disubstituted N-nitrosoureas showed a coarse correlation between alkylating activity and SCE induction in Chinese hamster V 79-E cells. On the other hand, this correlation is missing in the case of NCA, which is a potent SCE inducer despite relatively low alkylating activity. DMPNU is the strongest SCE inducer, but this compound shows a high stability in aqueous solution and, consequently, we were not able to detect an alkylating activity.
D000477:Alkylating Agents / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004355:Drug Stability; D005038:Ethylnitrosourea / Q000494:pharmacology; D008168:Lung; D008770:Methylnitrosourea / Q000494:pharmacology; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D012854:Sister Chromatid Exchange; D012996:Solutions; D013329:Structure-Activity Relationship
D000477:Alkylating Agents; D009607:Nitrosourea Compounds; D012996:Solutions; D008770:Methylnitrosourea; D005038:Ethylnitrosourea