Structure activity relationship of epoxides: different mutagenicity of the two diastereoisomeric 3-bromo-1,2-epoxycyclohexanes.
The mutagenic activities in V79 Chinese hamster cells and the alkylating abilities towards nicotinamide of the two diastereisomeric cis and trans-3-bromo-1,2-epoxycyclohexanes were measured and compared with those of unsubstituted 1,2-epoxycyclohexane and bromocyclohexane. trans-3-Bromo-1,2-epoxycyclohexane exhibited a mutagenic activity 2.5 times higher than that of its cis diastereoisomer, but very similar to that of the parent unbrominated epoxide, whereas the electrophilic reactivities towards nicotinamide were very similar for the three epoxides tested. Bromocyclohexane showed the highest toxicity, but no alkylating ability. The presence of an epoxide hydrolase activity in the V79 Chinese hamster cells used in the mutagenesis tests has been demonstrated using safrole oxide as the substrate, cis-3-Bromo-1,2-epoxycyclohexane, but not its trans diastereoisomer, is hydrolyzed by the enzyme present in microsomal preparations from the V79 cells. The results indicate that for the cycloaliphatic compounds examined: (1) the introduction of a bromide substituent at the carbon adjacent to the oxirane ring does not cause an increase in mutagenicity, (2) the relative stereochemical configuration at the above carbon does affect the biological activity and (3) the significantly different mutagenicity of the two diastereoisomeric 3-bromo-1,2-epoxycyclohexanes is not attributable to a different electrophilic reactivity, but could be related to some specific interaction with detoxifying enzymes present in the V79 Chinese hamster cells used in the biological experiments.
D000478:Alkylation; D000818:Animals; D001711:Biotransformation; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D003510:Cyclohexanes / Q000633:toxicity*; D007700:Kinetics; D008168:Lung; D008861:Microsomes / Q000378:metabolism; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D009536:Niacinamide; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D003510:Cyclohexanes; D009153:Mutagens; D009536:Niacinamide; C032834:3-bromo-1,2-epoxycyclohexane