Structure-activity relationship of mutagenic aromatic and heteroaromatic nitro compounds. Correlation with molecular orbital energies and hydrophobicity

Abstract

A review of the literature yielded data on over 200 aromatic and heteroaromatic nitro compounds tested for mutagenicity in the Ames test using S. typhimurium TA98. From the data, a quantitative structure-activity relationship (QSAR) has been derived for 188 congeners. The main determinants of mutagenicity are the hydrophobicity (modeled by octanol/water partition coefficients) and the energies of the lowest unoccupied molecular orbitals calculated using the AM1 method. It is also shown that chemicals possessing three or more fused rings possess much greater mutagenic potency than compounds with one or two fused rings. Since the QSAR is based on a very wide range in structural variation, aromatic rings from benzene to coronene are included as well as many different types of heterocycles, it is a significant step toward a predictive toxicology of value in the design of less mutagenic bioactive compounds.