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关于1,2,3-和1,2,4-三唑衍生物作为α-淀粉酶和α-葡萄糖苷酶抑制剂的药用特性的见解。

An insight on medicinal attributes of 1,2,3- and 1,2,4-triazole derivatives as alpha-amylase and alpha-glucosidase inhibitors.

作者信息

Sharma Anushka, Dubey Rahul, Bhupal Ritu, Patel Preeti, Verma Sant Kumar, Kaya Savas, Asati Vivek

机构信息

Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga, Punjab, India.

Health Services Vocational School, Department of Pharmacy, Sivas Cumhuriyet University, 58140, Sivas, Turkey.

出版信息

Mol Divers. 2024 Oct;28(5):3605-3634. doi: 10.1007/s11030-023-10728-1. Epub 2023 Sep 21.

Abstract

Diabetes Mellitus (DM) is the globe's common leading disease which is caused by high consumption of glucose. DM compiles groups of metabolic disorders which are characterized by inadequate secretion of insulin from pancreas, resulting in hyperglycemia condition. Many enzymes play a vital role in the metabolism of carbohydrate known as α-amylase and α-glucosidase which is calcium metalloenzyme that leads to breakdown of complex polysaccharides into glucose. To tackle this problem, search for newer antidiabetic drugs is the utmost need for the treatment and/or management of increasing diabetic burden. The inhibition of α-amylase and α-glucosidase is one of the effective therapeutic approaches for the development of antidiabetic therapeutics. The exhaustive literature survey has shown the importance of medicinally privileged triazole specifically 1,2,3-triazol and 1,2,4-triazoles scaffold tethered, fused and/or clubbed with other heterocyclic rings structures as promising agents for designing and development of novel antidiabetic therapeutics. Molecular hybrids namely pyridazine-triazole, pyrazoline-triazole, benzothiazole-triazole, benzimidazole-triazole, curcumin-triazole, (bis)coumarin-triazole, acridine-9-carboxamide linked triazole, quinazolinone-triazole, xanthone-triazole, thiazolo-triazole, thiosemicarbazide-triazole, and indole clubbed-triazole are few examples which have shown promising antidiabetic activity by inhibiting α-amylase and/or α-glucosidase. The present review summarizes the structure-activity relationship (SAR), enzyme inhibitory activity including IC values, percentage inhibition, kinetic studies, molecular docking studies, and patents filed of the both scaffolds as alpha-amylase and alpha-glucosidase inhibitors, which may be used for further development of potent inhibitors against both enzymes.

摘要

糖尿病(DM)是全球常见的主要疾病,由高糖消耗引起。DM包括一组代谢紊乱,其特征是胰腺胰岛素分泌不足,导致血糖升高。许多酶在碳水化合物代谢中起着至关重要的作用,如α-淀粉酶和α-葡萄糖苷酶,它们是钙金属酶,可导致复杂多糖分解为葡萄糖。为了解决这个问题,寻找新型抗糖尿病药物是治疗和/或管理日益增加的糖尿病负担的迫切需求。抑制α-淀粉酶和α-葡萄糖苷酶是开发抗糖尿病治疗药物的有效治疗方法之一。详尽的文献调查表明,具有药用特权的三唑,特别是1,2,3-三唑和1,2,4-三唑支架与其他杂环结构相连、融合和/或组合,作为设计和开发新型抗糖尿病治疗药物的有前景的药物。分子杂化物,如哒嗪-三唑、吡唑啉-三唑、苯并噻唑-三唑、苯并咪唑-三唑、姜黄素-三唑、(双)香豆素-三唑、吖啶-9-甲酰胺连接的三唑、喹唑啉酮-三唑、呫吨酮-三唑、噻唑并-三唑、硫代氨基脲-三唑和吲哚组合的三唑,是少数通过抑制α-淀粉酶和/或α-葡萄糖苷酶显示出有前景的抗糖尿病活性的例子。本综述总结了作为α-淀粉酶和α-葡萄糖苷酶抑制剂的两种支架的构效关系(SAR)、酶抑制活性,包括IC值、抑制百分比、动力学研究、分子对接研究和专利申请情况,这些可用于进一步开发针对这两种酶的强效抑制剂。

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