在这项研究中,合成了11种新型的多氢喹啉酰基酰肼衍生物,表征和筛选它们的体外抗糖尿病和抗糖基化活性。七个化合物2a,2d,2i,2h,2j,2f,和2g表现出显著的α-淀粉酶抑制活性,IC50值为3.51±2.13至11.92±2.30μM。同样,六个化合物2d,2f,2h,2i,2j,与标准阿卡波糖相比,2g显示出有效的α-葡萄糖苷酶抑制活性。此外,八种衍生物2d,2g,2f,2j,2a,2i,2g,与标准芦丁(IC50=22.5±0.90µM)相比,2e显示出优异的抗糖化活性,IC50值为6.91±2.66至15.80±1.87µM。进行分子对接以预测所有化合物与α-淀粉酶和α-葡糖苷酶的结合模式。对接分析表明,大多数化合物与α-淀粉酶和α-葡萄糖苷酶建立了强相互作用。所有化合物都能很好地适应α-淀粉酶和α-葡糖苷酶的结合袋。在所有化合物中,基于分别针对α-淀粉酶和α-葡糖苷酶的对接评分-8.2515和-7.3949,2a和2f是最有效的。这些结果为开发针对控制糖尿病个体餐后葡萄糖水平的新型候选物提供了希望。
In this study, eleven novel acyl hydrazides derivative of polyhydroquinoline were synthesized, characterized and screened for their in vitro anti-diabetic and anti-glycating activities. Seven compounds 2a, 2d, 2i, 2 h, 2j, 2f, and 2 g exhibited notable α-amylase inhibitory activity having IC50 values from 3.51 ± 2.13 to 11.92 ± 2.30 µM. Similarly, six compounds 2d, 2f, 2 h, 2i, 2j, and 2 g displayed potent α-glucosidase inhibitory activity compared to the standard acarbose. Moreover, eight derivatives 2d, 2 g, 2f, 2j, 2a, 2i, 2 g, and 2e showed excellent anti-glycating activity with IC50 values from 6.91 ± 2.66 to 15.80 ± 1.87 µM when compared them with the standard rutin (IC50 = 22.5 ± 0.90 µM). Molecular docking was carried out to predict the binding modes of all the compounds with α-amylase and α-glucosidase. The docking analysis revealed that most of the compounds established strong interactions with α-amylase and α-glucosidase. All compounds fitted well into the binding pockets of α-amylase and α-glucosidase. Among all compounds 2a and 2f were most potent based on docking score -8.2515 and -7.3949 against α-amylase and α-glucosidase respectively. These results hold promise for the development of novel candidates targeted at controlling postprandial glucose levels in individuals with diabetes.