Jha Ritesh, Goyal Kamya, Mehan Sidharth, Singh Gurpreet
Department of Pharmaceutical Chemistry, ISF College of Pharmacy, GT Road, Ghal Kalan, Moga 142001, Punjab, India.
Department of Pharmacology, ISF College of Pharmacy, GT Road, Ghal Kalan, Moga 142001, Punjab, India.
Bioorg Chem. 2025 Aug;163:108762. doi: 10.1016/j.bioorg.2025.108762. Epub 2025 Jul 18.
Diabetes mellitus (DM) is a chronic metabolic disorder characterised by elevated blood glucose levels resulting from insufficient insulin production or insulin resistance. Its global prevalence has surged, particularly in low- and middle-income countries, with over 830 million affected. In recent years, dual inhibition of α-amylase and α-glucosidase, the enzymes involved in the metabolism of complex polysaccharides, has gained visibility in anti-diabetic medication research. The inhibition of these enzymes is responsible for reducing postprandial hyperglycemia. FDA-approved drugs, acarbose, voglibose, and miglitol, are effective but have serious side effects. Many research papers from various research groups have appeared in different databases, from natural to synthetic resources, describing the dual inhibition of α-amylase and α-glucosidase. However, none of the molecules have advanced to clinical development. The current review focuses on compiling an exhaustive report of novel molecules derived from synthetic and natural resources that act as dual α-amylase and α-glucosidase inhibitors. The review also highlights their biological activity, selectivity, structure-activity relationship, molecular docking, and mechanistic studies. A special emphasis on drug-designing strategies has also been given in the manuscript. The comprehensive compilation of research work in the field will provide an inevitable scope for designing and developing novel adenosine inhibitors with improved selectivity and efficacy.
糖尿病（DM）是一种慢性代谢紊乱疾病，其特征是由于胰岛素分泌不足或胰岛素抵抗导致血糖水平升高。它在全球的患病率激增，尤其是在低收入和中等收入国家，超过8.3亿人受到影响。近年来，对参与复合多糖代谢的α-淀粉酶和α-葡萄糖苷酶的双重抑制在抗糖尿病药物研究中受到关注。抑制这些酶可降低餐后高血糖。美国食品药品监督管理局（FDA）批准的药物阿卡波糖、伏格列波糖和米格列醇有效，但有严重的副作用。来自不同研究小组的许多研究论文出现在不同的数据库中，从天然资源到合成资源，描述了α-淀粉酶和α-葡萄糖苷酶的双重抑制。然而，没有一种分子进入临床开发阶段。当前的综述重点是汇编一份详尽的报告，介绍来自合成和天然资源的新型分子，这些分子可作为双重α-淀粉酶和α-葡萄糖苷酶抑制剂。该综述还强调了它们的生物活性、选择性、构效关系、分子对接和机理研究。手稿中还特别强调了药物设计策略。该领域研究工作的全面汇编将为设计和开发具有更高选择性和疗效的新型腺苷抑制剂提供必然的空间。
