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糖尿病的管理——天然产物对抗二肽基肽酶-4、α-葡萄糖苷酶和钠依赖性葡萄糖共转运蛋白 2(SGLT2)的重要作用。

The management of diabetes mellitus-imperative role of natural products against dipeptidyl peptidase-4, α-glucosidase and sodium-dependent glucose co-transporter 2 (SGLT2).

机构信息

Università degli Studi di Firenze, NEUROFARBA Dept., Sezione di Scienze Farmaceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Florence), Italy; Department of Biological Sciences and Chemistry, University of Nizwa, Birkat Al-Mauz, P.O.Box 33, Nizwa 616, Oman; Natural and Medical Sciences Research Center, University of Nizwa, PC 616, Nizwa, Oman.

Natural and Medical Sciences Research Center, University of Nizwa, PC 616, Nizwa, Oman.

出版信息

Bioorg Chem. 2019 May;86:305-315. doi: 10.1016/j.bioorg.2019.02.009. Epub 2019 Feb 4.

Abstract

Diabetes mellitus is a chronic metabolic disorder which is rapidly spreading worldwide. It is characterized by persistent elevated blood glucose level above normal values (hyperglycemia) due to defect in either insulin secretion or in insulin action or both of them. Currently approved oral synthetic antidiabetic drugs such as biguanides, thiazolidinediones, sulfonylureas, and meglitinides have shown undesirable side effects. Therefore, newer approaches and targets for the management of diabetes mellitus are highly desirable. Dipeptidyl peptidase-4 enzyme, α-glucosidase enzyme and sodium-dependent glucose co-transporter 2 (SGLT2) have been recognized as effective therapeutic targets for the management of diabetes mellitus while natural products are alternatives to oral synthetic hypoglycemic agents. During the last two decades, many researchers were working on the identification and the validation of plant-derived products for curing various diseases. Natural products do not only provide useful drugs in their own right but also provide templates for the development of more effective compounds for enhanced therapeutic potential. Herein, we advocated the vital role of natural products as source of new drugs by presenting promising inhibitors of dipeptidyle peptidase-4 enzyme, α-glucosidase enzyme and (SGLT2) obtained from different medicinal plants as potential candidates for drug development against diabetes mellitus. The structure-activity relationship (SAR) of these various inhibitors is also discussed.

摘要

糖尿病是一种在全球范围内迅速蔓延的慢性代谢性疾病。其特征是由于胰岛素分泌或作用缺陷或两者兼而有之,导致血糖水平持续高于正常水平(高血糖)。目前批准的口服合成抗糖尿病药物,如双胍类、噻唑烷二酮类、磺酰脲类和格列奈类,已显示出不良的副作用。因此,非常需要新的方法和靶点来管理糖尿病。二肽基肽酶-4 酶、α-葡萄糖苷酶和钠依赖性葡萄糖共转运蛋白 2(SGLT2)已被认为是管理糖尿病的有效治疗靶点,而天然产物则是口服合成降血糖药物的替代品。在过去的二十年中,许多研究人员致力于鉴定和验证植物源性产品,以治疗各种疾病。天然产物不仅本身提供有用的药物,而且还为开发更有效的化合物提供模板,以提高治疗潜力。在此,我们通过介绍从不同药用植物中获得的有前途的二肽基肽酶-4 酶、α-葡萄糖苷酶和(SGLT2)抑制剂,强调了天然产物作为新药来源的重要作用,这些抑制剂可作为开发治疗糖尿病的潜在候选药物。还讨论了这些各种抑制剂的结构-活性关系(SAR)。

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