在 2 型糖尿病治疗中开发α-葡萄糖苷酶和α-淀粉酶抑制剂的最新进展:从硅学到体外研究的启示。

IF 3 4区 医学 Q2 PHARMACOLOGY & PHARMACY Current drug targets Pub Date : 2024-08-08 DOI:10.2174/0113894501313365240722100902
Fariya Khan, Mohsin Vahid Khan, Ajay Kumar, Salman Akhtar
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引用次数: 0

摘要

糖尿病是一种由高血糖引起的代谢紊乱疾病,会导致糖尿病神经病变和心血管疾病等严重威胁。控制餐后高血糖最可靠的措施之一是通过抑制消化系统中的酶(如α-葡萄糖苷酶和α-淀粉酶)来降低葡萄糖水平。在此,我们研究了如何使用抑制剂来抑制碳水化合物代谢,从而限制糖尿病患者的血糖水平。阿卡波糖、伏格列波糖和米格列醇是美国食品及药物管理局(FDA)批准的三种抑制剂,它们能有效抑制这两种酶,从而最大限度地降低高血糖,而且对降低心血管疾病的风险也有显著帮助。我们还将深入介绍目前市场上已知的其他抑制剂。与其他抑制剂相关的不良反应突出表明,在开发治疗 2 型糖尿病的更有效、更安全的强效抑制剂时,需要进行最新的硅学筛选和体外验证。最近的研究结果表明,α-葡萄糖苷酶和α-淀粉酶在碳水化合物代谢和引发葡萄糖水平升高方面发挥着重要作用。本综述介绍了与这两种酶有关的最新科学文献发现,以及作为潜在候选药物的一级和二级抑制剂的作用。此外,这篇综述还阐述了作用机制的框架、提取这些酶的不同植物来源以及抑制剂的动力学测定和它们之间的相互作用,这些都可在未来用于开发抗击 2 型糖尿病的潜在线索。
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Recent Advances in the Development of Alpha-Glucosidase and Alpha-Amylase Inhibitors in Type 2 Diabetes Management: Insights from In silico to In vitro Studies.

Diabetes is a metabolic disorder caused by high glucose levels, leading to serious threats such as diabetic neuropathy and cardiovascular diseases. One of the most reliable measures for controlling postprandial hyperglycemia is to reduce the glucose level by inhibiting enzymes in the digestive system, such as Alpha-Glucosidase and Alpha-Amylase. Here, we have investigated the use of inhibitors to inhibit carbohydrate metabolism in order to restrict glucose levels in diabetic patients. Acarbose, Voglibose, and Miglitol are three inhibitors approved by the FDA that efficiently inhibit these two enzymes and thereby minimising hyperglycemia but are al-so significantly helpful in reducing the risk of cardiovascular effects. We also provide insight into the other known inhibitors currently available in the market. The adverse effects associated with other inhibitors emphasise the demand for the latest in silico screening and in vitro validation in the development of potent inhibitors with greater efficacy and safety for the treatment of Type 2 diabetes. The recent findings suggest that Alpha-Glucosidase and Alpha-Amylase play a major role in carbohydrate metabolism and triggering the increase in glucose levels. This review pro-vides the latest scientific literature findings related to these two enzymes as well as the role of primary and secondary inhibitors as potential candidates. Moreover, this review elaborates the framework on the mechanism of action, different plant sources of extraction of these enzymes, as well as kinetic assay of inhibitors and their interaction that can be used in future prospects to de-velop potential leads to combat Type 2 diabetes.

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来源期刊
Current drug targets
Current drug targets 医学-药学
CiteScore
6.20
自引率
0.00%
发文量
127
审稿时长
3-8 weeks
期刊介绍: Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Current Drug Targets publishes guest edited thematic issues written by leaders in the field covering a range of current topics of drug targets. The journal also accepts for publication mini- & full-length review articles and drug clinical trial studies. As the discovery, identification, characterization and validation of novel human drug targets for drug discovery continues to grow; this journal is essential reading for all pharmaceutical scientists involved in drug discovery and development.
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