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 (eta) and absolute electronegativity (chi) (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 eta-chi 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.