Benzophenone-1 and -2 UV-filters potently inhibit human, rat, and mouse gonadal 3β-hydroxysteroid dehydrogenases: structure-activity relationship and in silico docking analysis

doi:10.1016/j.jsbmb.2023.106279

科研成果详情

题名	Benzophenone-1 and -2 UV-filters potently inhibit human, rat, and mouse gonadal 3β-hydroxysteroid dehydrogenases: structure-activity relationship and in silico docking analysis
作者	Wang, Mengyun1; Yu, Yang1; Tang, Yunbing2; Pan, Chengshuang1,3; Fei, Qianjin3; Hu, Zhiyan1; Li, Huitao1; Zhu, Yang 1; Wang, Yiyan1; Ge, Ren-shan1,2
发表日期	2023-06
发表期刊	The Journal of steroid biochemistry and molecular biology 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	3β-HSD isoforms Benzophenone UV-filters Docking Gonad Inhibition Progesterone
其他关键词	3-BETA-HYDROXYSTEROID DEHYDROGENASE ; URINARY CONCENTRATIONS ; VITRO
摘要	Benzophenone (BP) ultraviolet (UV) -filters have been widely used to prevent adverse effects of UV. Whether they can disrupt gonadal steroidogenesis remains unclear. Gonadal 3β-hydroxysteroid dehydrogenases (3β-HSD) catalyse the conversion of pregnenolone to progesterone. This study explored the effect of 12 BPs on human, rat, and mouse 3β-HSD isoforms, and analysed the structure-activity relationship (SAR) and underlying mechanisms. The inhibitory potency was BP-1 (IC50, 5.66±0.95 μM) > BP-2 (5.84±2.22 μM) > BP-6 (185.8±115.2 μM) > BP3-BP12 on human KGN 3β-HSD2, BP-2 (5.90±1.02 μM) > BP-1 (7.55±1.26 μM) > BP3-B12 on rat testicular 3β-HSD1, and BP-1 (15.04±5.20 μM) > BP-2 (22.64±11.81 μM) > BP-6（125.1±34.65 μM）> BP-7 (161.1±102.4 μM) > other BPs on mouse testicular 3β-HSD6. BP-1 is a mixed inhibitor of human, rat, and mouse 3β-HSDs, and BP-2 is a mixed inhibitor of human and rat 3β-HSDs and a noncompetitive inhibitor of mouse 3β-HSD6. 4-Hydroxyl substitution in the benzene ring plays a key role in enhancing potency of inhibiting human, rat, and mouse gonadal 3β-HSDs. BP-1 and BP-2 can penetrate human KGN cells to inhibit progesterone secretion at ≥10 μM. Docking analysis revealed that the 4-hydroxyl group of BP-1 and BP-2 forms hydrogen bonds with residue Ser123 of human 3β-HSD2 and residue Asp127 of rat 3β-HSD1. In conclusion, this study demonstrates that BP-1 and BP-2 are the most potent inhibitors of human, rat, and mouse gonadal 3β-HSDs and that there is a significant SAR difference
资助项目	Department of Health of Zhejiang Province [11-CX29]
出版者	PERGAMON-ELSEVIER SCIENCE LTD
ISSN	0960-0760
EISSN	1879-1220
卷号	230
DOI	10.1016/j.jsbmb.2023.106279
页数	13
WOS类目	Biochemistry & Molecular Biology ; Endocrinology & Metabolism
WOS研究方向	Biochemistry & Molecular Biology ; Endocrinology & Metabolism
WOS记录号	WOS:000961258600001
收录类别	PUBMED ; SCIE ; SCOPUS
在线发表日期	2023-03
URL	查看原文
PubMed ID	36871834
SCOPUSEID	2-s2.0-85150808562
通讯作者地址	[Wang, Yiyan]Department of Anaesthesiology,the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325027,China ; [Ge, Ren-shan]Department of Anaesthesiology,the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325027,China
Scopus学科分类	Endocrinology, Diabetes and Metabolism;Biochemistry;Molecular Medicine;Molecular Biology;Endocrinology;Clinical Biochemistry;Cell Biology
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/172912
专题	第二临床医学院、附属第二医院、育英儿童医院附属第一医院第一临床医学院（信息与工程学院）、附属第一医院_妇产科学_生殖医学中心
通讯作者	Wang, Yiyan; Ge, Ren-shan
作者单位	1.Department of Anaesthesiology,the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325027,China; 2.Department of Obstetrics and Gynecology,the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325027,China; 3.Reproductive Medicine Center,First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China
第一作者单位	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
通讯作者单位	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
第一作者的第一单位	第二临床医学院，附属第二医院、育英儿童医院
推荐引用方式 GB/T 7714	Wang, Mengyun,Yu, Yang,Tang, Yunbing,et al. Benzophenone-1 and -2 UV-filters potently inhibit human, rat, and mouse gonadal 3β-hydroxysteroid dehydrogenases: structure-activity relationship and in silico docking analysis[J]. The Journal of steroid biochemistry and molecular biology,2023,230.
APA	Wang, Mengyun., Yu, Yang., Tang, Yunbing., Pan, Chengshuang., Fei, Qianjin., ... & Ge, Ren-shan. (2023). Benzophenone-1 and -2 UV-filters potently inhibit human, rat, and mouse gonadal 3β-hydroxysteroid dehydrogenases: structure-activity relationship and in silico docking analysis. The Journal of steroid biochemistry and molecular biology, 230.
MLA	Wang, Mengyun,et al."Benzophenone-1 and -2 UV-filters potently inhibit human, rat, and mouse gonadal 3β-hydroxysteroid dehydrogenases: structure-activity relationship and in silico docking analysis".The Journal of steroid biochemistry and molecular biology 230(2023).