Structural determinants of parabens in inhibiting human and rat gonadal 3β-hydroxysteroid dehydrogenase

doi:10.1016/j.taap.2024.117133

科研成果详情

题名	Structural determinants of parabens in inhibiting human and rat gonadal 3β-hydroxysteroid dehydrogenase
作者	Chentao Ding1; He Zhu 1; Yunbing Tang2; Yingfen Ying2; Yang Zhu1; Han Lin 1; Ren-Shan Ge3; Huitao Li4
发表日期	2024-10-23
发表期刊	Toxicology and applied pharmacology 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	3β-HSD Docking analysis KGN cells Parabens Progesterone
摘要	This study delved into the impacts of 10 parabens on the activity of human and rat gonadal 3β-hydroxysteroid dehydrogenase (3β-HSD) within human KGN cell and rat testicular microsomes, as well as on the secretion of progesterone in KGN cells and the inhibitory potency was compared between human and rats. Intriguingly, the outcomes revealed that ethyl, propyl, butyl, hexyl, heptyl, nonyl, phenyl, and benzyl parabens displayed varying IC50 values for human 3β-HSD2, from 4.15 to 139.96 μM, demonstrating characteristics of mixed inhibitors. Notably, within KGN cells, all examined parabens, excluding nonyl and phenyl parabens, significantly inhibited progesterone secretion at 5-50 μM. In the case of rats, the IC50 values for these parabens on gonadal 3β-HSD1 fluctuated between 7.15 and 110.76 μM, likewise functioning as mixed inhibitors. Through docking analysis, it was proposed that most parabens effectively bind to NAD+ and/or steroid binding site. Moreover, bivariate correlation analysis unveiled an inverse correlation between IC50 values and structural characteristics such as LogP, molecular weight, heavy atom number, and carbon number within the alcohol moiety of parabens. 3D-QSAR elucidated pivotal regions, comprising hydrogen bond donor, hydrogen bond acceptor, and hydrophobic region, with the most potent inhibitor nonyl paraben engaging with all regions, while the weakest inhibitor ethyl paraben interacted with the regions except for the hydrophobic region. In conclusion, this investigation underscored the inhibitory effects imparted by several parabens on both human and rat gonadal 3β-HSD activity, with their inhibitory potency being modulated by aspects of hydrophobicity and carbon chain length
ISSN	0041-008X
EISSN	1096-0333
DOI	10.1016/j.taap.2024.117133
收录类别	PUBMED
URL	查看原文
PubMed ID	39454967
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/221015
专题	附属第二医院第二临床医学院、附属第二医院、育英儿童医院附属第二医院_妇产科
作者单位	1.Department of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital and Yuying Children's Hospital, Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.; 2.Department of Obstetrics and Gynecology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.; 3.Department of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital and Yuying Children's Hospital, Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Department of Obstetrics and Gynecology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Male Health and Environment of Wenzhou, 325000, Zhejiang Province, China. Electronic address: renshan_ge@wmu.edu.cn.; 4.Department of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital and Yuying Children's Hospital, Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. Electronic address: lihuitao@wmu.edu.cn.
第一作者单位	附属第二医院
第一作者的第一单位	附属第二医院
推荐引用方式 GB/T 7714	Chentao Ding,He Zhu,Yunbing Tang,et al. Structural determinants of parabens in inhibiting human and rat gonadal 3β-hydroxysteroid dehydrogenase[J]. Toxicology and applied pharmacology,2024.
APA	Chentao Ding., He Zhu., Yunbing Tang., Yingfen Ying., Yang Zhu., ... & Huitao Li. (2024). Structural determinants of parabens in inhibiting human and rat gonadal 3β-hydroxysteroid dehydrogenase. Toxicology and applied pharmacology.
MLA	Chentao Ding,et al."Structural determinants of parabens in inhibiting human and rat gonadal 3β-hydroxysteroid dehydrogenase".Toxicology and applied pharmacology (2024).