Hasaninezhad Fatemeh, Tavaf Zohreh, Panahi Farhad, Nourisefat Maryam, Khalafi-Nezhad Ali, Yousefi Reza
Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran.
Department of Chemistry, College of Sciences, Shiraz University, Shiraz, Iran.
J Diabetes Metab Disord. 2020 Nov 12;19(2):1505-1515. doi: 10.1007/s40200-020-00685-z. eCollection 2020 Dec.
Diabetes mellitus is a metabolic disorder characterized by high blood glucose levels and instability in carbohydrate metabolism. For treating diabetes, one important therapeutic approach is reducing the postprandial hyperglycemia which can be managed by delaying the absorption of glucose through inhibition of the carbohydrate-hydrolyzing enzymes, α-amylase (α-Amy) and α-glucosidase (α-Gls) in the digestive tract. In this work, a new class of curcumin derivatives incorporating pyrano[2,3-d]pyrimidine heterocycles was synthesized using a multicomponent reaction between curcumin, aldehydes, and barbituric acid. Using UV-Vis spectroscopic method, the synthetic compounds were assessed for their inhibitory properties against α-Amy and α-Gls enzymes. Also, the antioxidant potential of these compounds was measured spectroscopically and compared with Trolox which is known as a gold standard to measure antioxidant capacity. The results of present study suggest that the curcumin derivatives were able to efficiently inhibit both yeast and mammalian α-Gls. In comparison with the antidiabetic medicine acarbose, the synthetic curcumin derivatives were also capable to inhibit more effectively the yeast α-Gls. The partial inhibitory effects of these compounds against pancreatic α-Amy were also important in the terms of avoiding development of the possible gastrointestinal side effects. Moreover, some of the curcumin derivatives indicated stronger antioxidant activity than Trolox. Overall, these synthetic curcumin analogues might be considered as novel molecular templates for development of efficient antidiabetic compounds with promising inhibitory activities against α-Amy and α-Gls enzymes.
The online version contains supplementary material available at 10.1007/s40200-020-00685-z.
糖尿病是一种以高血糖水平和碳水化合物代谢不稳定为特征的代谢紊乱疾病。对于糖尿病的治疗，一种重要的治疗方法是降低餐后高血糖，这可以通过抑制消化道中的碳水化合物水解酶α-淀粉酶（α-Amy）和α-葡萄糖苷酶（α-Gls）来延迟葡萄糖的吸收来实现。在这项工作中，通过姜黄素、醛和巴比妥酸之间的多组分反应合成了一类新的含有吡喃并[2,3-d]嘧啶杂环的姜黄素衍生物。使用紫外可见光谱法评估了合成化合物对α-Amy和α-Gls酶的抑制特性。此外，通过光谱法测量了这些化合物的抗氧化潜力，并与作为测量抗氧化能力金标准的曲洛昔康进行了比较。本研究结果表明，姜黄素衍生物能够有效抑制酵母和哺乳动物的α-Gls。与抗糖尿病药物阿卡波糖相比，合成的姜黄素衍生物也能够更有效地抑制酵母α-Gls。这些化合物对胰腺α-Amy的部分抑制作用在避免可能的胃肠道副作用方面也很重要。此外，一些姜黄素衍生物显示出比曲洛昔康更强的抗氧化活性。总体而言，这些合成的姜黄素类似物可被视为开发具有对α-Amy和α-Gls酶有前景抑制活性的高效抗糖尿病化合物的新型分子模板。
在线版本包含可在10.1007/s40200-020-00685-z获取的补充材料。
