Discovery of Potential Inhibitors of Aldosterone Synthase from Chinese Herbs Using Pharmacophore Modeling, Molecular Docking, and Molecular Dynamics Simulation Studies.
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...
| Publicado en: | BioMed Research International Vol. 2016; pp. 1 - 9 |
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| Autores principales: | , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
10/3/2016
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=118500661&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 118500661 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23146133 FT2T jtl: BioMed Research International issn: 23146133 maglogo: N pubinfo: dt: 10/3/2016 vid: 2016 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 118500661 118500661 118500661 10.1155/2016/4182595 118500661 ppf: 1 ppct: 8 formats: fmt: @attributes: type: P tig: atl: Discovery of Potential Inhibitors of Aldosterone Synthase from Chinese Herbs Using Pharmacophore Modeling, Molecular Docking, and Molecular Dynamics Simulation Studies. aug: au: Luo, Ganggang Lu, Fang Qiao, Liansheng Chen, Xi Li, Gongyu Zhang, Yanling affil: Beijing Key Laboratory of TCM Foundation and New Drug Research, School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100102, China sug: subj: Oxidoreductases Antagonists and Inhibitors Drugs, Chinese Herbal Analysis Models, Theoretical Simulations Aldosterone Pharmacophore Hypertension Drug Therapy Validity Molecular Structure Resource Databases Imidazoles Analysis Acids Analysis Descriptive Statistics Funding Source ab: 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. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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