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对从异叶翅子树果实中提取的化合物与腺苷酸激酶-胰岛素受体进行的计算机对接研究。

Insilico docking study of compounds elucidated from helicteres isora fruits with ampkinase- insulin receptor.

作者信息

Vennila Subramanium, Bupesh Giridharan, Saravanamurali Krishnan, SenthilKumar Viajayan, SenthilRaja Ramalingam, Saran Natarajan, Magesh Sachidanandam

机构信息

King Institute of Preventive Medicine and Research, Guindy, Chennai-600032.

出版信息

Bioinformation. 2014 May 20;10(5):263-6. doi: 10.6026/97320630010263. eCollection 2014.

Abstract

Insulin receptor (IR) proteins were essential intracellular signaling peptides in the insulin action cascade. Insulin receptor substrate proteins (IRS-1and IRS-2) serve and regulate the insulin level in the normal insulin action. The broad role of IRS-1 and IRS-2 in cell growth and survival reveals a common regulatory pathway linking development, somatic growth, fertility, neuronal proliferation, and aging to the core mechanisms used by vertebrates for nutrient sensing. Such type of proteins were cyclic adenosine monophosphate-activated protein kinase, this proteins play a key role in the insulin response and regulation. Type -2 Diabetes mellitus occurs during prolonged periods of peripheral insulin resistance due to inactivation of IRS proteins. The compounds isolated from the medicinal plants were safer than synthetic drugs and possess high bio activity. In the present study, four compounds were elucidated from fruits of Helicteres isora. The elucidated compounds were evaluated for the antidiabetic activity using in silico docking study. The receptor was analyzed for the active site and pocket finder tools. The aminoacids such as Phenylalanine, Lysine, Glutamic acid and Asparigine were predicted as active site binding residues. Docking studies were done through Autodock 4 software. All the compounds from fruits of Helicteres isora showed good docking profiles with AMP Kinase, except compound-3 (1,2,3,4-tetrahydro-1,5,6,8-tetramethyl-7-(2-methylprop-1-enylnaphthalene-4-ylpivalate). Finally the result from the study demonstrates that the HS-1, HS-2 and HS-4 posses potent anti diabetic activity against type-2 diabetes mellitus through drug action on AMP kinase cascade system.

摘要

胰岛素受体(IR)蛋白是胰岛素作用级联反应中重要的细胞内信号肽。胰岛素受体底物蛋白(IRS - 1和IRS - 2)在正常胰岛素作用中发挥作用并调节胰岛素水平。IRS - 1和IRS - 2在细胞生长和存活中的广泛作用揭示了一条将发育、体细胞生长、生育能力、神经元增殖和衰老与脊椎动物用于营养感知的核心机制联系起来的共同调节途径。这类蛋白有环磷酸腺苷激活蛋白激酶,该蛋白在胰岛素反应和调节中起关键作用。2型糖尿病是由于IRS蛋白失活导致外周胰岛素抵抗长期存在而发生的。从药用植物中分离出的化合物比合成药物更安全且具有高生物活性。在本研究中,从异叶翅子树果实中鉴定出四种化合物。使用计算机对接研究对鉴定出的化合物进行抗糖尿病活性评估。对受体进行活性位点分析和口袋查找工具分析。预测苯丙氨酸、赖氨酸、谷氨酸和天冬酰胺等氨基酸为活性位点结合残基。通过Autodock 4软件进行对接研究。异叶翅子树果实中的所有化合物与AMP激酶都显示出良好的对接图谱,除了化合物 - 3(1,2,3,4 - 四氢 - 1,5,6,8 - 四甲基 - 7 - (2 - 甲基丙 - 1 - 烯基)萘 - 4 - 基新戊酸酯)。最后,该研究结果表明,HS - 1、HS - 2和HS - 4通过作用于AMP激酶级联系统对2型糖尿病具有有效的抗糖尿病活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/637b/4070034/5db9b0992096/97320630010263F1.jpg

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