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.
Kobayashi
Shigeki
S
Department of Analytical Chemistry of Medicines, Showa Pharmaceutical University, Tokyo, Japan. kobayasi@ac.shoyaku.ac.jp
Shinohara
Hidemi
H
Tabata
Kyoko
K
Yamamoto
Naoko
N
Miyai
Akira
A
D001559:Benzhydryl Compounds; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D004968:Estrogens, Non-Steroidal / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D010636:Phenols / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013997:Time Factors; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004968:Estrogens, Non-Steroidal; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds