Title
Novel small molecule 11β-HSD1 inhibitor from the endophytic fungus Penicillium commune
Author
Weiguang Sun, Xintao Chen, Qingyi Tong, Hucheng Zhu, Yan He, Liang Lei, Yongbo Xue, Guangmin Yao, Zengwei Luo, Jianping Wang, Hua Li, Yonghui Zhang
Year
2016
Journal
Scientific Reports
Abstract
Two new phenone derivatives penicophenones A (1) and B (2), a new cyclic tetrapeptide penicopeptide A (3), and five known compounds were isolated from the culture broth of Penicillium commune, an endophytic fungus derived from Vitis vinifera. Compounds 1–3 were elucidated by extensive spectroscopic analyses including 1D and 2D NMR and HRESIMS. The absolute configurations of 1 and 3 were determined by comparing its ECD with related molecules and modified Marfey’s analysis, respectively. Penicophenone A (1) possesses a rare benzannulated 6,6-spiroketal moiety, which is a new member of the unusual structural class with peniphenone A as the representative. Compound 3 exhibited significant inhibition activities against 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in vitro and showed strong binding affinity to 11β-HSD1. Moreover, compound 3 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 compound 3coordinated in the active site of 11β-HSD1 is essential for the ability of diminishing the enzyme activity.
Full Article
Instrument
J-810
Keywords
Circular dichroism, Absolute configuration, Medicinal