title: Novel small molecule 11β-HSD1 inhibitor from the endophytic fungus Penicillium commune.
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 3 coordinated in the active site of 11β-HSD1 is essential for the ability of diminishing the enzyme activity.
authors.affiliation: 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.
authors.forename: Weiguang
authors.initials: W
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Xintao
authors.initials: X
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Tong
authors.affiliation: 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.
authors.forename: Hucheng
authors.initials: H
authors.lastname: Zhu
authors.affiliation: 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.
authors.forename: Yan
authors.initials: Y
authors.lastname: He
authors.affiliation: Puai Hospital Affliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Lei
authors.affiliation: 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.
authors.forename: Yongbo
authors.initials: Y
authors.lastname: Xue
authors.affiliation: 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.
authors.forename: Guangmin
authors.initials: G
authors.lastname: Yao
authors.affiliation: 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.
authors.forename: Zengwei
authors.initials: Z
authors.lastname: Luo
authors.affiliation: 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.
authors.forename: Jianping
authors.initials: J
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D020134:Catalytic Domain / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005656:Fungal Proteins / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D010407:Penicillium / Q000254:growth & development* / Q000378:metabolism; D027843:Vitis / Q000382:microbiology
chemical_list: D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D009842:Oligopeptides; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1