Stereo Structure-Controlled and Electronic Structure-Controlled Estrogen-Like Chemicals to Design and Develop Non-estrogenic Bisphenol A Analogs Based on Chemical Hardness Concept

The aim of this study was to elucidate the structure–activity relationship of bisphenol A (BPA) analogs using absolute hardness (η) and absolute electronegativity (χ) (chemical hardness) and to design a non-estrogen active BPA. To determine the structure–activity relationships of BPA analogs, we investigated MCF-7 cell proliferation stimulated by BPA analogs and an η–χ diagram based on the electronic structure of the BPA analogs. The results show that the actions of the environmental hormones BPA analogs have two chemical properties; (i) ‘stereo structure-controlled’ and (ii) ‘electronic structure-controlled’ estrogen-like chemical activities. Therefore, we designed and synthesized BPA analogs which do not possess these 2 characteristics, ((i) and (ii)), and demonstrate the non-estrogen activity of the analog.