利用 Docking 设计和计算评估用于抑制单酰基甘油脂肪酶的新型氨基甲酸酯衍生物

Abhishek Kashyap, Dimpy Rani, Suresh Kumar, Shailendra Bhatt
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引用次数: 0

摘要

研究发现,人类的各种疾病和生理过程都与单酰基甘油脂肪酶有关,如疼痛、炎症和神经退行性疾病。这种酶的重量为 33 KDa,是一种丝氨酸水解酶。据报道,这种酶存在于中枢和外周神经系统中,并显示出其作为内源性大麻素信号网络系统中关键信号因子的重要性。据报道,该酶还是癌细胞和肿瘤生长及其增殖的游离脂肪酸提供者。在增殖的癌细胞中,可以观察到单酰基甘油脂肪酶活性的增加。研究还发现,癌细胞的生长、迁移和存活与磷脂酸、溶血磷脂酸、磷酸鞘磷脂和前列腺素 E2 有关。研究还发现,这些物质与癌细胞的生长、传播和存活能力有关,并随着酶活性的增加而增加。在本研究中,我们对新设计的含有氨基甲酸酯特征的单酰基甘油抑制剂进行了计算筛选研究,这些分子是在以前开发的单酰基甘油氨基甲酸酯抑制剂的基础上设计的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Design and Computational Evaluation of New Carbamate Derivatives for the Inhibition of Monoacylglycerol Lipase Enzyme by using Docking
Different disorders and physiological process have been found to be associated with monoacylglycerol lipase enzyme in humans, like pain, inflammation, and neurodegenerative diseases also. The enzyme is a 33 KDa in weight and a type of serine hydrolase enzyme in nature. The presence of enzyme has been reported in both central and peripheral nervous systems and has show its importance as a key signalling factor in endocannabinoid signalling network system. The enzyme has also reported as source of free fatty acid provider for the cancer cell and tumor growth and their proliferation. In proliferative cancer cells, increased the monoacylglycerol lipase activity is observed. The growth, migration and survival of cancer cells have also found to be associated with phosphatidic acid, lysophosphatidic acid, sphingosine phosphate and prostaglandin E2, which are act as signalling molecules and are found to be derived from free fatty acid. These are also found to be related to the growth, transmission and viability of cancer cells, which increases with the enzyme activity. In the present study we performing computation screening studies of newly designed monoacylglycerol inhibitors which contains carbamate features, these molecules are designed based on previously developed monoacylglycerol carbamate inhibitors
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