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天然低血糖生成生物活性物质:新途径与新可能。

Natural hypoglycaemic bioactives: Newer avenues and newer possibilities.

机构信息

Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Ajmer, Rajasthan, India.

出版信息

Phytother Res. 2024 Sep;38(9):4428-4452. doi: 10.1002/ptr.8281. Epub 2024 Jul 11.

Abstract

The incidences of endocrine and metabolic disorders like diabetes have increased worldwide. Several proposed molecular pathways mechanisms for the management of diabetes have been identified, but glycaemic control is still a challenging task in the drug discovery process. Most of the drug discovery processes lead to numerous scaffolds that are prominent in natural products. The review deals with the natural bioactives as an α-amylase inhibitors, α-glucosidase inhibitors, protein tyrosine phosphatase-1B inhibitors, dipeptidyl peptidase-IV inhibitors, G-protein coupled receptors-40 agonists, PPAR-γ agonists and the activators of 5'-adenosine monophosphate-activated protein kinase and glucokinase. So, in this review, we focused on the hypoglycaemic bioactives, which will assist scientific developers, traditional medicinal practitioners, and readers to discover some potent antidiabetic molecules. Strategies like chemometric approaches, scaffold hopping, and total synthesis of natural products by group modification or ring opening/closing mechanism could be useful for the development of novel hit/lead antidiabetic molecules. The study concludes that each phyto molecule inherits a potential to get explored by repurposing techniques for various antidiabetic targets and offer an alternative antidiabetic therapeutic medicinal potential.

摘要

全球范围内,内分泌和代谢紊乱(如糖尿病)的发病率不断上升。目前已经确定了几种用于管理糖尿病的分子途径机制,但血糖控制仍然是药物发现过程中的一项具有挑战性的任务。大多数药物发现过程都会产生许多突出的天然产物骨架。本综述涉及天然生物活性物质作为α-淀粉酶抑制剂、α-葡萄糖苷酶抑制剂、蛋白酪氨酸磷酸酶-1B 抑制剂、二肽基肽酶-IV 抑制剂、G 蛋白偶联受体-40 激动剂、PPAR-γ 激动剂和 5'-腺苷单磷酸激活蛋白激酶和葡萄糖激酶的激活剂。因此,在本综述中,我们重点介绍了具有降血糖作用的生物活性物质,这将有助于科学开发者、传统医学从业者和读者发现一些有效的抗糖尿病分子。化学计量学方法、骨架跳跃以及通过基团修饰或开环/闭环机制对天然产物进行全合成等策略,可能有助于开发新型的抗糖尿病命中/先导分子。研究结论表明,每种植物分子都有可能通过重新利用技术针对各种抗糖尿病靶点进行探索,并提供一种替代的抗糖尿病治疗药物潜力。

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