CinnaGen Medical Biotechnology Research Center, Alborz University of Medical Sciences, Karaj, Iran.
Department of Medicinal Chemistry, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran.
Arch Pharm (Weinheim). 2021 Dec;354(12):e2100179. doi: 10.1002/ardp.202100179. Epub 2021 Aug 31.
Thirteen new phenoxy-biscoumarin-N-phenylacetamide derivatives (7a-m) were designed based on a molecular hybridization approach as new α-glucosidase inhibitors. These compounds were synthesized with high yields and evaluated in vitro for their inhibitory activity against yeast α-glucosidase. The obtained results revealed that a significant proportion of the synthesized compounds showed considerable α-glucosidase-inhibitory activity in comparison to acarbose as a positive control. Representatively, 2-(4-(bis(4-hydroxy-2-oxo-2H-chromen-3-yl)methyl)phenoxy)-N-(4-bromophenyl)acetamide (7f), with IC = 41.73 ± 0.38 µM against α-glucosidase, was around 18 times more potent than acarbose (IC = 750.0 ± 10.0 µM). This compound was a competitive α-glucosidase inhibitor. Molecular modeling and dynamic simulation of these compounds confirmed the obtained results through in vitro experiments. Prediction of the druglikeness/ADME/toxicity of the compound 7f and comparison with the standard drug acarbose showed that the new compound 7f was probably better than the standard drug in terms of toxicity.
基于分子杂交方法，我们设计了 13 种新的苯氧基双香豆素-N-苯乙酰胺衍生物（7a-m）作为新型α-葡萄糖苷酶抑制剂。这些化合物以高产率合成，并在体外评估其对酵母α-葡萄糖苷酶的抑制活性。所得结果表明，与阳性对照阿卡波糖相比，相当一部分合成化合物表现出相当大的α-葡萄糖苷酶抑制活性。代表性的是，2-(4-(双(4-羟基-2-氧代-2H-色烯-3-基)甲基)苯氧基)-N-(4-溴苯基)乙酰胺（7f）对α-葡萄糖苷酶的 IC = 41.73 ± 0.38 µM，比阿卡波糖（IC = 750.0 ± 10.0 µM）强约 18 倍。该化合物是一种竞争性α-葡萄糖苷酶抑制剂。这些化合物的分子建模和动态模拟通过体外实验证实了所得结果。对化合物 7f 的药物性质/ADME/毒性进行预测，并与标准药物阿卡波糖进行比较表明，新化合物 7f 在毒性方面可能优于标准药物。
