Structural Analysis of a Group of Phytoestrogens for the Presence of a 2-D Geometric Descriptor Associated with Non-genotoxic Carcinogens and Some Estrogens

Abstract

Abstract

Analysis of a group of phytoestrogens indicates that the majority of these chemicals are devoid of a 6Å distance descriptor biophore. This 6Å biophore is associated with the carcinogenicity of a set of chemicals in the mouse subset of the Carcinogenic Potency Database assembled by Gold et al. The prevalence of non-DNA-reactive carcinogens and chemicals endowed with estrogenic activity included in the group of chemicals possessing 6Å descriptor suggests that it describes a ligand binding site on an estrogen receptor. Evidence is presented that estrogens with and without the 6Å biophore bind to alternate receptors or to similar receptors but with different affinities. Since the 6Å biophore was identified based upon a carcinogenicity database, it is conceivable that binding to the putative receptor that recognizes this biophore is associated with carcinogenicity. Alternatively, estrogens devoid of this 6Å biophore may be noncarcinogenic, suggesting that carcinogenicity and estrogenicity may be separate phenomena.