title: Discovery of Potential Inhibitors of Aldosterone Synthase from Chinese Herbs Using Pharmacophore Modeling, Molecular Docking, and Molecular Dynamics Simulation Studies.
abstract: Aldosterone synthase (CYP11B2) is a key enzyme for the biosynthesis of aldosterone, which plays a significant role for the regulation of blood pressure. Excess aldosterone can cause the dysregulation of the renin-angiotensin-aldosterone system (RAAS) and lead to hypertension. Therefore, research and development of CYP11B2 inhibitor are regarded as a novel approach for the treatment of hypertension. In this study, the pharmacophore models of CYP11B2 inhibitors were generated and the optimal model was used to identify potential CYP11B2 inhibitors from the Traditional Chinese Medicine Database (TCMD, Version 2009). The hits were further refined by molecular docking and the interactions between compounds and CYP11B2 were analyzed. Compounds with high Fitvalue, high docking score, and expected interactions with key residues were selected as potential CYP11B2 inhibitors. Two most promising compounds, ethyl caffeate and labiatenic acid, with high Fitvalue and docking score were reserved for molecular dynamics (MD) study. All of them have stability of ligand binding which suggested that they might perform the inhibitory effect on CYP11B2. This study provided candidates for novel drug-like CYP11B2 inhibitors by molecular simulation methods for the hypertension treatment.
authors: Beijing Key Laboratory of TCM Foundation and New Drug Research, School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100102, China.
authors: Ganggang
authors: 0000-0002-4175-2263
authors: G
authors: Luo
authors: Beijing Key Laboratory of TCM Foundation and New Drug Research, School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100102, China.
authors: Fang
authors: F
authors: Lu
authors: Beijing Key Laboratory of TCM Foundation and New Drug Research, School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100102, China.
authors: Liansheng
authors: L
authors: Qiao
authors: Beijing Key Laboratory of TCM Foundation and New Drug Research, School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100102, China.
authors: Xi
authors: X
authors: Chen
authors: Beijing Key Laboratory of TCM Foundation and New Drug Research, School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100102, China.
authors: Gongyu
authors: G
authors: Li
authors: Beijing Key Laboratory of TCM Foundation and New Drug Research, School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100102, China.
authors: Yanling
authors: 0000-0001-6344-8804
authors: Y
authors: Zhang
mesh_terms: D000450:Aldosterone / Q000096:biosynthesis / Q000737:chemistry; D001665:Binding Sites; D002109:Caffeic Acids / Q000737:chemistry / Q000494:pharmacology; D019405:Cytochrome P-450 CYP11B2 / Q000037:antagonists & inhibitors / Q000737:chemistry*; D004365:Drugs, Chinese Herbal / Q000737:chemistry* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D008516:Medicine, Chinese Traditional; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D011485:Protein Binding
chemical_list: D002109:Caffeic Acids; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D008024:Ligands; D000450:Aldosterone; C032773:ethyl caffeate; D019405:Cytochrome P-450 CYP11B2