Citrinal B, natural 11 beta-hydroxysteroid dehydrogennase type 1 inhibitor identified from structure-based virtual screening

Jie Cao; Limin Gao; Yizhan Chen; Weiguang Sun; Fuqian Wang; Hua Li; Yonghui Zhang

doi:10.1016/j.fitote.2017.09.018

Citrinal B, natural 11 beta-hydroxysteroid dehydrogennase type 1 inhibitor identified from structure-based virtual screening

Fitoterapia. 2017 Nov:123:29-34. doi: 10.1016/j.fitote.2017.09.018. Epub 2017 Sep 28.

Authors

Jie Cao¹, Limin Gao¹, Yizhan Chen², Weiguang Sun³, Fuqian Wang⁴, Hua Li⁵, Yonghui Zhang⁶

Affiliations

¹ Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
² Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
³ Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
⁴ Department of Pharmacy, Wuhan First Hospital, Wuhan 430022, China.
⁵ Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: li_hua@hust.edu.cn.
⁶ Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: zhangyh@mails.tjmu.edu.cn.

PMID: 28962943
DOI: 10.1016/j.fitote.2017.09.018

Abstract

Citrinal B, a tricyclic compound from endophytic fungus Colletotrichum capsici in our previous studies, exhibited significant inhibitory activity against 11β-hydroxysteroid dehydrogenase type 1 (11 β-HSD1) in vitro and showed strong binding affinity to 11β-HSD1. Moreover, citrinal B treatments decreased the lipid droplet accumulation associate with the inhibition of 11β-HSD1 expression in differentiate induced 3T3-L1 preadipocytes. Furthermore, the molecular docking demonstrated that citrinal B coordinated in the active site of 11β-HSD1 is essential for the ability of diminishing the enzyme activity.

Keywords: 11 β-HSD1 inhibitor; Citrinal B; Natural product; Virtual screening.

MeSH terms

11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors*
3T3-L1 Cells
Animals
Colletotrichum / chemistry*
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / isolation & purification
Hep G2 Cells
Heterocyclic Compounds, 3-Ring / chemistry*
Heterocyclic Compounds, 3-Ring / isolation & purification
Humans
Lipid Metabolism / drug effects
Mice
Molecular Docking Simulation

Substances

Enzyme Inhibitors
Heterocyclic Compounds, 3-Ring
citrinal B
11-beta-Hydroxysteroid Dehydrogenase Type 1