Bisphenol a alternatives suppress human and rat aromatase activity: QSAR structure-activity relationship and in silico docking analysis

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作   者：

Xia M.;  Zheng J.;  Chen S.;  Tang Y.;  Wang S.;  Ji Z.;  Hao T.;  Li H.;  Li L.;  Ge R.-S.;  Liu Y.; 

作者机构：

Department of Gynecology and Obstetrics The Second Affiliated Hospital and Yuying Children's; 

关键词：

Human placenta;  Bisphenols;  Aromatase;  LogP;  Docking analysis; 

期刊名称：

Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research

i s s n：

0278-6915

年卷期：

2024 年 183 卷

页   码：

114257-114257

页   码：

摘   要：

? 2023The use of alternative substances to replace bisphenol A (BPA) has been encouraged. The objective of this study was to evaluate the effects of BPA and 9 BPA alternatives on human and rat aromatase (CYP19A1) in human and rat placental microsomes. The results revealed that bisphenol A, AP, B, C, E, F, FL, S, and Z, and 4,4′-thiodiphenol (TDP) inhibited human CYP19A1 and bisphenol A, AP, B, C, FL, Z, and TDP inhibited rat CYP19A1. The IC50 values of human CYP19A1 ranged from 3.3 to 172.63 μM and those of rat CYP19A1 ranged from 2.20 to over 100 μM. BPA alternatives were mixed/competitive inhibitors and inhibited estradiol production in BeWo placental cells. Molecular docking analysis showed that BPA alternatives bind to the domain between heme and steroid and form a hydrogen bond with catalytic residue Met374. Pharmacophore analysis showed that there were one hydrogen bond donor, one hydrophobic region, and one ring aromatic hydrophobic region. Bivariate correlation analysis showed that molecular weight, alkyl atom weight, and LogP of BPA alternatives were inversely correlated with their IC50 values. In conclusion, BPA alternatives can inhibit human and rat CYP19A1 and the lipophilicity and the substituted alkyl size determines their inhibitory strength.