One of the therapeutic approaches in the management of type 2 diabetes is delaying the glucose absorption through α-glucosidase enzyme inhibition, which can reduce the occurrence of postprandial hyperglycemia. Based on this thought, a series of novel chloro-substituted 2-(2-methyl-1-phenyl-1H-pyrrol-3-yl)-2-oxo-N-(pyridin-3-yl) acetamide derivatives 5a–i were synthesized and their α-glucosidase inhibitory activities were evaluated. All the synthesized compounds have shown moderate to excellent in vitro α-glucosidase inhibitory activity with IC₅₀ values in the range of 111–673 µM) as compared to acarbose, the standard drug (750 ± 9 µM). Compound 5e (111 ± 12 µM), among the series, was the most potent inhibitor of α-glucosidase in a competitive mode of action based on the kinetic study. The molecular docking study of compounds 5e and 5a revealed that they have a lower free binding energy (− 4.27 kcal/mol and − 3.17 kcal/mol, respectively) than acarbose (− 2.47 kcal/mol), which indicates that the target compound binds more easily to the enzyme than acarbose does. The outcomes from the molecular docking studies supported the results obtained from the in vitro assay. In conclusion, the overall results of our study reveal that the synthesized compounds could be a potential candidate in the search for novel α-glucosidase inhibitors to manage postprandial hyperglycemia incidence.

中文翻译：

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2-（2-甲基-1H-吡咯-3-基）-2-氧代-N-（吡啶-3-基）乙酰胺衍生物的合成和生物学评价：体外α-葡萄糖苷酶抑制作用以及动力学和分子对接研究

治疗2型糖尿病的治疗方法之一是通过抑制α-葡萄糖苷酶来延迟葡萄糖的吸收，这可以减少餐后高血糖的发生。基于这一思想，一系列新的氯取代的2-（2-甲基-1-苯基-1H-吡咯-3-基）-2-氧代-N-（吡啶-3-基）乙酰胺衍生物5a – i合成了α-葡糖苷酶抑制活性。与标准药物阿卡波糖（750±9 µM）相比，所有合成的化合物均显示出中等至优异的体外α-葡萄糖苷酶抑制活性，IC ₅₀值在111–673 µM范围内。化合物5e根据动力学研究，在一系列竞争性作用方式中，（111±12 µM）是最有效的α-葡萄糖苷酶抑制剂。化合物5e和5a的分子对接研究表明，与阿卡波糖（-2.47 kcal / mol）相比，它们具有较低的自由结合能（分别为-4.27 kcal / mol和-3.17 kcal / mol），这表明目标化合物与比阿卡波糖更容易吸收酶。分子对接研究的结果支持了体外测定的结果。总之，我们研究的总体结果表明，合成的化合物可能是寻找新型α-葡萄糖苷酶抑制剂来管理餐后高血糖发生率的潜在候选者。