Radiosensitizing ability and cytotoxicity of some 5(4)-substituted 2-methyl-4(5)-nitroimidazoles.

Radiosensitizing efficiency and cytotoxicity of three 2-methyl-4(5)-nitroimidazoles substituted with electron-withdrawal groups -NO2, -Cl and -OCH3 in 5(4)-position ("ortho" position) have been evaluated in vitro on V 79-379 A cells under aerobic as well as under hypoxic conditions. It has been established that 2-h incubation of cells at 37 degrees C in the presence of increasing (up to 2 mM) concentration of the compounds causes a moderate cytotoxicity for P7(2-methyl-5(4)-chloro-4(5)-nitroimidazole) and P5(2-methyl-4,5-dinitroimidazole). Cytotoxicities of these compounds are much stronger under hypoxic than under aerobic conditions. The compound P9(2-methyl-5(4)-methoxy-4(5)-nitroimidazole) is practically completely nontoxic. The radiosensitizing efficiency of P5, P7, and P9 at 2 mM concentration expressed by ER (enhancement ratio) equals 1.75, 1.57 and 1.14 respectively. A discussion regarding the features of electron-affinity, cytotoxicity and radiosensitizing ability of the compounds studied is presented.