Benzophenone-type ultraviolet filters inhibit human and rat placental 3β-hydroxysteroid dehydrogenases: Structure-activity relationship and in silico docking analysis

doi:10.1016/j.toxlet.2023.05.006

科研成果详情

题名	Benzophenone-type ultraviolet filters inhibit human and rat placental 3β-hydroxysteroid dehydrogenases: Structure-activity relationship and in silico docking analysis
作者	Lin, Hao 1; Wang, Shaowei2; Tang, Yunbing2; Hu, Zhiyan1; Chen, Xiaofang 3; Li, Huitao1; Zhu, Yang1; Wang, Yiyan1; Liu, Yi 2; Ge, Ren-shan1,2,3
发表日期	2023-06-01
发表期刊	Toxicology letters 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	3β-HSD Benzophenone Docking analysis Inhibition Placenta Progesterone
其他关键词	3-BETA-HYDROXYSTEROID DEHYDROGENASE ; UV FILTERS ; DATABASE ; PREDICTION ; CATALYSIS ; CELLS ; VITRO
摘要	Benzophenones (BPs) are a class of chemicals found in various personal care and cosmetic products, such as sunscreens and lotions. Their usage is known to cause reproductive and hormonal health risks, but the exact mechanism of action remains unknown. In this study, we investigated the effects of BPs on human and rat placental 3β-hydroxysteroid dehydrogenases (3β-HSDs), which play a crucial role in the biosynthesis of steroid hormones, particularly progesterone. We tested inhibitory effects of 12 BPs, and performed structure-activity relationship (SAR) and in silico docking analysis. The potency of BPs to inhibit human 3β-HSD1 (h3β-HSD1) is BP-1 (IC50, 8.37 μM)>BP-2 (9.06 μM)>BP-12 (94.24 μM)>BP-7 (1160 μM) >BP-8 (1257 μM) >BP-6 (1410 μM) > other BPs (ineffective at 100 μM). The potency of BPs on rat r3β-HSD4 is BP-1 (IC50, 4.31 μM)>BP-2 (117.3 μM)>BP-6 (669 μM) >BP-3 (820 μM)>other BPs (ineffective at 100 μM). BP-1, BP-2, and BP-12 are mixed h3β-HSD1 inhibitors and BP-1 is a mixed r3β-HSD4 inhibitor. LogP, lowest binding energy, and molecular weight were positively associated with IC50 for h3β-HSD1, while LogS was negatively associated with IC50. The 4-OH substitution in the benzene ring plays a key role in enhancing the effectiveness of inhibiting h3β-HSD1 and r3β-HSD4, possibly through increasing water solubility and decreasing lipophilicity by forming hydrogen bonds. BP-1 and BP-2 inhibited progesterone production in human JAr cells. Docking analysis shows that 2-OH of BP-1 forms hydrogen bonds with catalytic residue Ser125 of h3β-HSD1 and Thr125 of r3β-HSD4. In conclusion, this study demonstrates that BP-1 and BP-2 are moderate inhibitors of h3β-HSD1 and BP-1 is a moderate inhibitor of r3β-HSD4. There is a significant SAR differences for 3β-HSD homologues between BPs and distinct species-dependent inhibition of placental 3β-HSDs
资助项目	Department of Health of Zhejiang Province[11-CX29];
出版者	ELSEVIER IRELAND LTD
ISSN	0378-4274
EISSN	1879-3169
卷号	382 页码:47-57
DOI	10.1016/j.toxlet.2023.05.006
页数	11
WOS类目	Toxicology
WOS研究方向	Toxicology
WOS记录号	WOS:001011660500001
收录类别	PUBMED ; SCIE ; SCOPUS
在线发表日期	2023-05
URL	查看原文
PubMed ID	37217011
SCOPUSEID	2-s2.0-85160411409
通讯作者地址	[Liu, Yi]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	Toxicology
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/180549
专题	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_麻醉重点学科实验室
通讯作者	Liu, Yi
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,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.Key Laboratory of Structural Malformations in Children of Zhejiang Province,Key Laboratory of Environment and Male Reproductive Medicine of Wenzhou,Zhejiang Province,325000,China
第一作者单位	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	附属第二医院
推荐引用方式 GB/T 7714	Lin, Hao,Wang, Shaowei,Tang, Yunbing,et al. Benzophenone-type ultraviolet filters inhibit human and rat placental 3β-hydroxysteroid dehydrogenases: Structure-activity relationship and in silico docking analysis[J]. Toxicology letters,2023,382:47-57.
APA	Lin, Hao., Wang, Shaowei., Tang, Yunbing., Hu, Zhiyan., Chen, Xiaofang., ... & Ge, Ren-shan. (2023). Benzophenone-type ultraviolet filters inhibit human and rat placental 3β-hydroxysteroid dehydrogenases: Structure-activity relationship and in silico docking analysis. Toxicology letters, 382, 47-57.
MLA	Lin, Hao,et al."Benzophenone-type ultraviolet filters inhibit human and rat placental 3β-hydroxysteroid dehydrogenases: Structure-activity relationship and in silico docking analysis".Toxicology letters 382(2023):47-57.