UV-filter benzophenones suppress human, pig, rat, and mouse 11β-hydroxysteroid dehydrogenase 1: Structure-activity relationship and in silico docking analysis

doi:10.1016/j.cbpc.2024.109900

科研成果详情

题名	UV-filter benzophenones suppress human, pig, rat, and mouse 11β-hydroxysteroid dehydrogenase 1: Structure-activity relationship and in silico docking analysis
作者	Hao, Ting1,2,3; Zhao, Xin 1,2,3; Ji, Zhongyao1,2,3; Xia, Miaomiao 1,2,3; Lu, Han1,4; Sang, Jianmin1,2,3; Wang, Shaowei1,4; Li, Linxi1,2,3; Ge, Ren-shan1,2,3,4; Zhu, Qiqi1,2,3,4
发表日期	2024-07
发表期刊	Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	11β-HSD1 Benzophenone Docking Glucocorticoid Metabolic activation
其他关键词	HEXOSE-6-PHOSPHATE DEHYDROGENASE ; 3-BETA-HYDROXYSTEROID DEHYDROGENASE ; ENDOCRINE DISRUPTORS ; TYPE-1 ; TISSUE ; STEROIDOGENESIS ; CONSEQUENCES ; INHIBITORS ; STRESS ; VITRO
摘要	Benzophenone chemicals (BPs) have been developed to prevent the adverse effects of UV radiation and they are widely contaminated. 11β-Hydroxysteroid dehydrogenase 1 (11β-HSD1) catalyze the conversion of inactive glucocorticoid to active glucocorticoid, playing critical role in many physiological function. However, the direct effect of BPs on human, pig, rat, and mouse 11β-HSD1 remains unclear. In this study, we screened the inhibitory strength of 12 BPs on 4 species, and performed the structure-activity relationship (SAR) and in silico docking analysis. The inhibitory potency of BPs was: for human 11β-HSD1, BP6 (IC50 = 18.76 μM) > BP8 (40.84 μM) > BP (88.89 μM) > other BPs; for pig 11β-HSD1, BP8 (45.57 μM) > BP6 (59.44 μM) > BP2 (65.12 μM) > BP (135.56 μM) > other BPs; for rat 11β-HSD1, BP7 (67.17 μM) > BP (68.83 μM) > BP8 (133.04 μM) > other BPs; and for mouse 11β-HSD1, BP8 (41.41 μM) > BP (50.61 μM) > other BPs. These BP chemicals were mixed/competitive inhibitors of these 11β-HSD1 enzymes. The 2,2'-dihydroxy substitutions in two benzene rings play a key role in enhancing the effectiveness of inhibiting 11β-HSD1, possibly via increasing hydrogen bond interactions. Docking analysis shows that these BPs bind to NADPH/glucocorticoid binding sites and forms hydrogen bonds with catalytic residues Ser and/or Tyr. In conclusion, this study demonstrates that BP chemicals can inhibit 11β-HSD1 from 4 species, and there are subtle species-dependent difference in the inhibitory strength and structural variations of BPs
资助项目	Zhejiang Provincial Nature Science Foundation[LY22H040010];
出版者	ELSEVIER SCIENCE INC
ISSN	1532-0456
EISSN	1878-1659
卷号	281
DOI	10.1016/j.cbpc.2024.109900
页数	14
WOS类目	Biochemistry & Molecular Biology ; Endocrinology & Metabolism ; Toxicology ; Zoology
WOS研究方向	Biochemistry & Molecular Biology ; Endocrinology & Metabolism ; Toxicology ; Zoology
WOS记录号	WOS:001223482500002
收录类别	PUBMED ; SCOPUS ; SCIE
URL	查看原文
PubMed ID	38518984
SCOPUSEID	2-s2.0-85189809148
通讯作者地址	[Li, Linxi]Key Laboratory of Pediatric Anesthesiology,Ministry of Education and Key Laboratory of Anesthesiology of Zhejiang Province,Wenzhou Medical University,Zhejiang,Wenzhou,325027,China ; [Ge, Ren-shan]Department of Anesthesiology and Perioperative Medicine,the Second Affiliated Hospital and Yuying Children's Hospital,Wenzhou Medical University,Zhejiang,Wenzhou,325027,China
Scopus学科分类	Biochemistry;Physiology;Aquatic Science;Animal Science and Zoology;Toxicology;Cell Biology;Health, Toxicology and Mutagenesis
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/210364
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	Li, Linxi; Ge, Ren-shan; Zhu, Qiqi
作者单位	1.Department of Anesthesiology and Perioperative Medicine,the Second Affiliated Hospital and Yuying Children's Hospital,Wenzhou Medical University,Zhejiang,Wenzhou,325027,China; 2.Key Laboratory of Pediatric Anesthesiology,Ministry of Education and Key Laboratory of Anesthesiology of Zhejiang Province,Wenzhou Medical University,Zhejiang,Wenzhou,325027,China; 3.Key Laboratory of Environment and Male Reproductive Medicine of Wenzhou,Key Laboratory of Structural Malformations in Children of Zhejiang Province,Zhejiang Province,Wenzhou,325000,China; 4.Department of Obstetrics and Gynecology,the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325027,China
第一作者单位	附属第二医院; 温州医科大学
通讯作者单位	温州医科大学; 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	Hao, Ting,Zhao, Xin,Ji, Zhongyao,et al. UV-filter benzophenones suppress human, pig, rat, and mouse 11β-hydroxysteroid dehydrogenase 1: Structure-activity relationship and in silico docking analysis[J]. Comparative biochemistry and physiology. Toxicology & pharmacology : CBP,2024,281.
APA	Hao, Ting., Zhao, Xin., Ji, Zhongyao., Xia, Miaomiao., Lu, Han., ... & Zhu, Qiqi. (2024). UV-filter benzophenones suppress human, pig, rat, and mouse 11β-hydroxysteroid dehydrogenase 1: Structure-activity relationship and in silico docking analysis. Comparative biochemistry and physiology. Toxicology & pharmacology : CBP, 281.
MLA	Hao, Ting,et al."UV-filter benzophenones suppress human, pig, rat, and mouse 11β-hydroxysteroid dehydrogenase 1: Structure-activity relationship and in silico docking analysis".Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 281(2024).