Demethoxylation of curcumin enhances its inhibition on human and rat 17β-hydroxysteroid dehydrogenase 3: QSAR structure-activity relationship and in silico docking analysis

doi:10.1016/j.fct.2024.114489

科研成果详情

题名	Demethoxylation of curcumin enhances its inhibition on human and rat 17β-hydroxysteroid dehydrogenase 3: QSAR structure-activity relationship and in silico docking analysis
作者	Ji, Zhongyao1,2,3,4; Sang, Jianmin1,2,3,4; Wang, Hong1,2,3,4; Xia, Miaomiao1,2,3,4; Hao, Ting1,2,3,4; Chen, Liping 1,2,3; Lu, Han1,2,3,4; Wang, Shaowei1,2,3,4; Yao, Ming 1,2,3; Li, Linxi1,2,3,4; Ge, Ren-shan1,2,3,5
发表日期	2024-04
发表期刊	Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	17β-HSD3 17β-hydroxysteroid dehydrogenase 3 Curcuminoids Molecular docking Structure-activity relationship
其他关键词	17-BETA-HYDROXYSTEROID-DEHYDROGENASE TYPE-III ; IDENTIFICATION ; DATABASE ; PROTEIN ; VITRO
摘要	Curcuminoids have many pharmacological effects. They or their metabolites may have side effects by suppressing 17β-hydroxysteroid dehydrogenase 3 (17β-HSD3). Herein, we investigated the inhibition of curcuminoids and their metabolites on human and rat 17β-HSD3 and analyzed their structure-activity relationship (SAR) and performed in silico docking. Curcuminoids and their metabolites ranked in terms of IC50 values against human 17β-HSD3 were bisdemethoxycurcumin (0.61 μM) > curcumin (8.63 μM) > demethoxycurcumin (9.59 μM) > tetrahydrocurcumin (22.04 μM) > cyclocurcumin (29.14 μM), and those against rat 17β-HSD3 were bisdemethoxycurcumin (3.94 μM) > demethoxycurcumin (4.98 μM) > curcumin (9.62 μM) > tetrahydrocurcumin (45.82 μM) > cyclocurcumin (143.5 μM). The aforementioned chemicals were mixed inhibitors for both enzymes. Molecular docking analysis revealed that they bind to the domain between the androstenedione and NADPH active sites of 17β-HSD3. Bivariate correlation analysis showed a positive correlation between LogP and pKa of curcumin derivatives with their IC50 values. Additionally, a 3D-QSAR analysis revealed that a pharmacophore model consisting of three hydrogen bond acceptor regions and one hydrogen bond donor region provided a better fit for bisdemethoxycurcumin compared to curcumin. In conclusion, curcuminoids and their metabolites possess the ability to inhibit androgen biosynthesis by directly targeting human and rat 17β-HSD3. The inhibitory strength of these compounds is influenced by their lipophilicity and ionization characteristics
资助项目	Zhejiang Provincial Health Department [11-CX29]
出版者	PERGAMON-ELSEVIER SCIENCE LTD
ISSN	0278-6915
EISSN	1873-6351
卷号	186
DOI	10.1016/j.fct.2024.114489
页数	13
WOS类目	Food Science & Technology ; Toxicology
WOS研究方向	Food Science & Technology ; Toxicology
WOS记录号	WOS:001186578900001
收录类别	PUBMED ; SCOPUS ; SCIE
URL	查看原文
PubMed ID	38360388
SCOPUSEID	2-s2.0-85185379517
通讯作者地址	[Ge, Ren-shan]Department of Anaesthesiology,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325027,China ; [Yao, Ming]Department of Anaesthesiology,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325027,China ; [Li, Linxi]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	Food Science;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/207631
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附属第二医院_麻醉重点学科实验室
通讯作者	Yao, Ming; Li, Linxi; Ge, Ren-shan
作者单位	1.Department of Anesthesiology and Perioperative Medicine,The Second Affiliated Hospital and Yuying Children's Hospital,Zhejiang,Wenzhou,325027,China; 2.Key Laboratory of Pediatric Anesthesiology,Ministry of Education,Zhejiang,Wenzhou,325027,China; 3.Key Laboratory of Anesthesiology of Zhejiang Province,Wenzhou Medical University,Zhejiang,Wenzhou,325027,China; 4.Department of Gynecology and Obstetrics,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325027,China; 5.Key Laboratory of Environment and Male Reproductive Medicine of Wenzhou,and Key Laboratory of Structural Malformations in Children of Zhejiang Province,Zhejiang Province,Wenzhou,325000,China
第一作者单位	温州医科大学; 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
推荐引用方式 GB/T 7714	Ji, Zhongyao,Sang, Jianmin,Wang, Hong,et al. Demethoxylation of curcumin enhances its inhibition on human and rat 17β-hydroxysteroid dehydrogenase 3: QSAR structure-activity relationship and in silico docking analysis[J]. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association,2024,186.
APA	Ji, Zhongyao., Sang, Jianmin., Wang, Hong., Xia, Miaomiao., Hao, Ting., ... & Ge, Ren-shan. (2024). Demethoxylation of curcumin enhances its inhibition on human and rat 17β-hydroxysteroid dehydrogenase 3: QSAR structure-activity relationship and in silico docking analysis. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 186.
MLA	Ji, Zhongyao,et al."Demethoxylation of curcumin enhances its inhibition on human and rat 17β-hydroxysteroid dehydrogenase 3: QSAR structure-activity relationship and in silico docking analysis".Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 186(2024).