PDF(Pubmed)
Abstract：
Aim: The purpose of this study is to design and synthesize a series of novel chalcone amide α-glucosidase (AG) inhibitors (L1-L10) based on virtual screening and molecular dynamics (MD) simulation. Materials & methods: Target compounds (L1-L10) were synthesized from 2-hydroxyacetophenone and methyl 4-formylbenzoate. Results: In vitro activity test shows that most compounds have good AG inhibition. Specially, compound L4 (IC50 = 8.28 ± 0.04 μM) had the best inhibitory activity, superior to positive control acarbose (IC50 = 8.36 ± 0.02 μM). Molecular docking results show that the good potency of L4 maybe attributed to strong interactions between chalcone skeleton and active site, and the torsion of carbon nitrogen bond in amide group. Conclusion: Compound L4 maybe regard as a good anti-Type II diabetes candidate to preform further study.
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[Box: see text].
摘要：
目的：本研究的目的是基于虚拟筛选和分子动力学（MD）模拟，设计并合成一系列新型的查耳酮酰胺α-葡萄糖苷酶（AG）抑制剂（L1-L10）。材料和方法:由2-羟基苯乙酮和4-甲酰苯甲酸甲酯合成目标化合物(L1-L10)。结果:体外活性测试表明,大多数化合物具有良好的AG抑制作用。特别是,化合物L4(IC50=8.28±0.04μM)具有最好的抑制活性,优于阳性对照阿卡波糖(IC50=8.36±0.02μM)。分子对接结果表明，L4的良好效力可能归因于查尔酮骨架与活性位点之间的强相互作用，以及酰胺基碳氮键的扭转。结论：化合物L4可能被视为良好的抗II型糖尿病候选药物，有待进一步研究。
[方框：见正文]。
[方框：见正文]。
