Pharmacophore-based discovery of FXR-agonists. Part II: Identification of bioactive triterpenes from Ganoderma lucidum
文献类型：期刊论文
| 作者 | Grienke, Ulrike5,6; Mihaly-Bison, Judit1; Schuster, Daniela3,5; Afonyushkin, Taras1; Binder, Markus1; Guan, Shu-hong4 ; Cheng, Chun-ru4; Wolber, Gerhard2; Stuppner, Hermann5,6; Guo, De-an4
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| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY
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| 出版日期 | 2011-11-15 |
| 卷号 | 19期号:22页码:6779-6791 |
| 关键词 | Farnesoid X receptor Ganoderma lucidum Lanostane triterpenes Ganoderic acids Molecular modeling Virtual screening Natural products |
| ISSN号 | 0968-0896 |
| DOI | 10.1016/j.bmc.2011.09.039 |
| 文献子类 | Article |
| 英文摘要 | The farnesoid X receptor (FXR) belonging to the metabolic subfamily of nuclear receptors is a ligand-induced transcriptional activator. Its central function is the physiological maintenance of bile acid homeostasis including the regulation of glucose and lipid metabolism. Accessible structural information about its ligand-binding domain renders FXR an attractive target for in silico approaches. Integrated to natural product research these computational tools assist to find novel bioactive compounds showing beneficial effects in prevention and treatment of, for example, the metabolic syndrome, dyslipidemia, atherosclerosis, and type 2 diabetes. Virtual screening experiments of our in-house Chinese Herbal Medicine database with structure-based pharmacophore models, previously generated and validated, revealed mainly lanostane-type triterpenes of the TCM fungus Ganoderma lucidum Karst. as putative FXR ligands. To verify the prediction of the in silico approach, two Ganoderma fruit body extracts and compounds isolated thereof were pharmacologically investigated. Pronounced FXR-inducing effects were observed for the extracts at a concentration of 100 mu g/mL. Intriguingly, five lanostanes out of 25 secondary metabolites from G. lucidum, that is, ergosterol peroxide (2), lucidumol A (11), ganoderic acid TR (12), ganodermanontriol (13), and ganoderiol F (14), dose-dependently induced FXR in the low micromolar range in a reporter gene assay. To rationalize the binding interactions, additional pharmacophore profiling and molecular docking studies were performed, which allowed establishing a first structure-activity relationship of the investigated triterpenes. (C) 2011 Elsevier Ltd. All rights reserved. |
| WOS关键词 | FARNESOID-X-RECEPTOR ; BILE-ACID RECEPTOR ; NATURAL-PRODUCT GUGGULSTERONE ; ORPHAN NUCLEAR RECEPTOR ; HYPERLIPIDEMIC RATS ; GENE-EXPRESSION ; MARINE SPONGE ; POTENT ; LIGAND ; ACTIVATION |
| 资助项目 | National Research Network (NFN)[S10703/S10711/S10713] ; Austrian Science Fund (FWF)[00000000] ; University of Innsbruck[00000000] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000296535900028 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278335]  |
| 专题 | 成果转移转化处 上海中药现代化研究中心 |
| 通讯作者 | Rollinger, Judith M. |
| 作者单位 | 1.Med Univ Vienna, Ctr Biomol Med & Pharmacol, Dept Vasc Biol & Thrombosis Res, A-1090 Vienna, Austria; 2.Free Univ Berlin, Inst Pharm Pharmaceut Chem, D-14195 Berlin, Germany 3.Univ Innsbruck, Comp Aided Mol Design Grp, Inst Pharm Pharmaceut Chem, A-6020 Innsbruck, Austria; 4.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 5.Univ Innsbruck, Ctr Mol Biosci Innsbruck, A-6020 Innsbruck, Austria; 6.Univ Innsbruck, Inst Pharm Pharmacognosy, A-6020 Innsbruck, Austria; |
| 推荐引用方式 GB/T 7714 | Grienke, Ulrike,Mihaly-Bison, Judit,Schuster, Daniela,et al. Pharmacophore-based discovery of FXR-agonists. Part II: Identification of bioactive triterpenes from Ganoderma lucidum[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2011,19(22):6779-6791. |
| APA | Grienke, Ulrike.,Mihaly-Bison, Judit.,Schuster, Daniela.,Afonyushkin, Taras.,Binder, Markus.,...&Rollinger, Judith M..(2011).Pharmacophore-based discovery of FXR-agonists. Part II: Identification of bioactive triterpenes from Ganoderma lucidum.BIOORGANIC & MEDICINAL CHEMISTRY,19(22),6779-6791. |
| MLA | Grienke, Ulrike,et al."Pharmacophore-based discovery of FXR-agonists. Part II: Identification of bioactive triterpenes from Ganoderma lucidum".BIOORGANIC & MEDICINAL CHEMISTRY 19.22(2011):6779-6791. |
入库方式： OAI收割
来源：上海药物研究所
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