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	Ding, Chentao1,2; Zhu, He 1,2; Tang, Yunbing 3,4; Ying, Yingfen 3,4; Zhu, Yang 1,2; Lin, Han1,2; Ge, Ren-Shan1,2,3,4,5; Li, Huitao1,2
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
其他关键词	HUMAN TYPE-1 ; CATALYSIS
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
资助项目	NFSC [82371610, 82301795]; Zhejiang Provincial Natural Science Foundation [LY22H040010, LQ22H040008]
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
ISSN	0041-008X
EISSN	1096-0333
卷号	492
DOI	10.1016/j.taap.2024.117133
页数	12
WOS类目	Pharmacology & Pharmacy ; Toxicology
WOS研究方向	Pharmacology & Pharmacy ; Toxicology
WOS记录号	WOS:001352974100001
收录类别	PUBMED ; SCIE ; SCOPUS
URL	查看原文
PubMed ID	39454967
SCOPUSEID	2-s2.0-85207594269
通讯作者地址	[Ge, Ren-Shan;Li, Huitao]Wenzhou Med Univ, Affiliated Hosp 2, Dept Anesthesiol & Perioperat Med, Wenzhou 325027, Zhejiang, Peoples R China. ; [Ge, Ren-Shan;Li, Huitao]Wenzhou Med Univ, Yuying Childrens Hosp, Key Lab Pediat Anesthesiol, Key Lab Anesthesiol Zhejiang Prov,Minist Educ, Wenzhou 325027, Zhejiang, Peoples R China.
Scopus学科分类	Toxicology;Pharmacology
SCOPUS_ID	SCOPUS_ID:85207594269
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	附属第一医院_麻醉科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_麻醉科
通讯作者	Ge, Ren-Shan; Li, Huitao
作者单位	1.Wenzhou Med Univ, Affiliated Hosp 2, Dept Anesthesiol & Perioperat Med, Wenzhou 325027, Zhejiang, Peoples R China; 2.Wenzhou Med Univ, Yuying Childrens Hosp, Key Lab Pediat Anesthesiol, Key Lab Anesthesiol Zhejiang Prov,Minist Educ, Wenzhou 325027, Zhejiang, Peoples R China; 3.Wenzhou Med Univ, Affiliated Hosp 2, Dept Obstet & Gynecol, Wenzhou 325027, Zhejiang, Peoples R China; 4.Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou 325027, Zhejiang, Peoples R China; 5.Key Lab Male Hlth & Environm Wenzhou, Wenzhou 325000, Zhejiang, Peoples R China
第一作者单位	附属第二医院_麻醉科; 第二临床医学院，附属第二医院、育英儿童医院
通讯作者单位	附属第二医院_麻醉科; 第二临床医学院，附属第二医院、育英儿童医院
第一作者的第一单位	附属第二医院_麻醉科
推荐引用方式 GB/T 7714	Ding, Chentao,Zhu, He,Tang, Yunbing,et al. Structural determinants of parabens in inhibiting human and rat gonadal 3β-hydroxysteroid dehydrogenase[J]. Toxicology and applied pharmacology,2024,492.
APA	Ding, Chentao., Zhu, He., Tang, Yunbing., Ying, Yingfen., Zhu, Yang., ... & Li, Huitao. (2024). Structural determinants of parabens in inhibiting human and rat gonadal 3β-hydroxysteroid dehydrogenase. Toxicology and applied pharmacology, 492.
MLA	Ding, Chentao,et al."Structural determinants of parabens in inhibiting human and rat gonadal 3β-hydroxysteroid dehydrogenase".Toxicology and applied pharmacology 492(2024).