Theoretical study of N-nitrosoureas and mechanism of their carcinogenic effect

A mechanistic study into the carcinogenic action of N-nitrosoureas (NU) was carried out with the aid of the semiempirical MINDO/3 method. The proposed reaction pathways of NU biodegradation mechanisms were examined and the most probable one was identified on the ground of theoretical considerations. The calculations of reaction enthalpies confirmed NU as SN1 reagents. The reactivity of a series of NU molecules (both isolated and under the solvent influence) were studied with respect to the detection of possible determinants of the relative carcinogenic potency. The correlations revealed a key function of the nitrosogroup and of the N3-C7 fragment in the decomposition process. The role of the transport properties and lipophilicity of parent NU molecules in the initial steps of the mechanism of carcinogenic effects was demonstrated as well.