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Design, synthesis and biological evaluation of novel phthalimide-Schiff base-coumarin hybrids as potent α-glucosidase inhibitors
Chemical Papers ( IF 2.1 ) Pub Date : 2020-06-15 , DOI: 10.1007/s11696-020-01246-7
Maedeh Sherafati , Maryam Mohammadi-Khanaposhtani , Shahram Moradi , Mohammad Sadegh Asgari , Nadia Najafabadipour , Mohammad Ali Faramarzi , Mohammad Mahdavi , Mahmood Biglar , Bagher Larijani , Haleh Hamedifar , Mir Hamed Hajimiri

We have designed and synthesized phthalimide-Schiff base-coumarin hybrids 8ab, 9ad, 10ab, and 11ad and evaluated them for α-glucosidase inhibitory potential against yeast form of this enzyme. For the synthesis of title compounds 4-hydroxybenzaldehyde, 4-hydroxy-3-methoxybenzaldehyde, 2-hydroxybenzaldehyde, 2-hydroxybenzaldehyde derivatives, coumarin-3-carbohydrazide, and coumarin-7-yloxy-acetohydrazide were used. In vitro α-glucosidase inhibition revealed that all the synthesized compounds exhibited outstanding α-glucosidase inhibition with IC50 values ranging between 85.2 ± 1.7 and 577.7 ± 7.5 µM when compared with the standard inhibitor acarbose having IC50 value 750.0 ± 12.0 µM. The most potent compounds were 4-hydroxybenzaldehyde derivative 8a with coumarin-3-carbohydrazide moiety, 2-hydroxy-5-nitrobenzaldehyde derivative 11d with coumarin-7-yloxy-acetohydrazide moiety, and 2-hydroxy-5-nitrobenzaldehyde derivative 9d with coumarin-3-carbohydrazide moiety. Molecular docking studies were carried out to understand the interaction modes and binding energies of the most active compounds and standard drug acarbose. This studies predicted that compounds 8a, 11d, and 9d (respectively with binding energies = − 10.77, − 8.65, and − 8.66 kcal/mol) bind to active site α-glucosidase more easily than acarbose (binding energy = − 4.04 kcal/mol).



中文翻译:

新型邻苯二甲酰亚胺-席夫碱-香豆素杂种作为有效的α-葡萄糖苷酶抑制剂的设计,合成和生物学评价

我们设计并合成了邻苯二甲酰亚胺-席夫碱-香豆素杂种8a - b9a - d10a - b11a - d,并评估了它们对这种酶的酵母形式的α-葡萄糖苷酶抑制潜力。为了合成标题化合物4-羟基苯甲醛,4-羟基-3-甲氧基苯甲醛,2-羟基苯甲醛,2-羟基苯甲醛衍生物,香豆素-3-碳酰肼和香豆素-7-酰氧基-乙酰肼。体外对α-葡萄糖苷酶的抑制作用表明,所有合成的化合物均对IC 50表现出出色的α-葡萄糖苷酶抑制作用与IC 50值为750.0±12.0 µM的标准抑制剂阿卡波糖相比,该值介于85.2±1.7至577.7±7.5 µM之间。最有效的化合物是带有香豆素-3-碳酰肼部分的4-羟基苯甲醛衍生物8a,带有香豆素-7-酰氧基-乙酰肼部分的2-羟基-5-硝基苯甲醛衍生物11d和带有香豆素-3-的2-羟基-5-硝基苯甲醛衍生物9d。 3-碳酰肼部分。进行了分子对接研究以了解最具活性的化合物与标准药物阿卡波糖的相互作用模式和结合能。这项研究预测化合物8a11d9d (分别具有结合能= − 10.77,− 8.65和− 8.66 kcal / mol)比阿卡波糖(结合能= − 4.04 kcal / mol)更容易结合至活性位点α-葡萄糖苷酶。

更新日期:2020-06-15
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