Cytotoxic activity and fragmentation of aziridines in microsomes

Abstract The fragmentation reaction of 2-para-substituted phenyl-N-methylaziridines in rat liver microsomes was studied. The relative reactivity against the substituent group, estimated from the amount of styrenes produced in liver microsomal solution, was para-Cl > para-Me > H > para-NO 2 > para-OMe. The cytotoxic activity of these aziridines was also studied using HeLa cells and L-1210 mouse leukemia cells in free-floating culture. The order of cytotoxic activity with HeLa and L-1210 cells was Cl  Me > H > NO 2  OMe and Me > Cl  OMe > H > NO 2 , respectively. The results indicated that the orders of cytotoxic activity and fragmentation reactivity for the parasubstituted aziridines have some parallel relationship. The nitrosomethane generated by fragmentation reaction of aziridine probably plays an important part in the biological activity of aziridines.