新型查尔酮酰胺α-葡萄糖苷酶抑制剂的设计、合成和抑制评估。

IF 3.2 4区医学 Q3 CHEMISTRY, MEDICINAL

Future medicinal chemistry Pub Date : 2024-07-02 Epub Date: 2024-05-22 DOI:10.1080/17568919.2024.2347092

Song Yao Lv, Li Ping Cheng

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引用次数: 0

摘要

目的：本研究旨在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查尔酮酰胺类α-葡萄糖苷酶（AG）抑制剂（L1-L10）。材料与方法：目标化合物（L1-L10）由 2-羟基苯乙酮和 4-甲酰基苯甲酸甲酯合成。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。其中，化合物 L4（IC50 = 8.28 ± 0.04 μM）的抑制活性最好，优于阳性对照阿卡波糖（IC50 = 8.36 ± 0.02 μM）。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，以及酰胺基团中碳氮键的扭转。结论化合物 L4 可能是一种很好的抗 II 型糖尿病候选化合物，有待进一步研究。

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Design, synthesis and inhibition evaluation of novel chalcone amide α-glucosidase inhibitors.

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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来源期刊

Future medicinal chemistry CHEMISTRY, MEDICINAL-

CiteScore

5.80

自引率

2.40%

发文量

118

审稿时长

4-8 weeks

期刊介绍： Future Medicinal Chemistry offers a forum for the rapid publication of original research and critical reviews of the latest milestones in the field. Strong emphasis is placed on ensuring that the journal stimulates awareness of issues that are anticipated to play an increasingly central role in influencing the future direction of pharmaceutical chemistry. Where relevant, contributions are also actively encouraged on areas as diverse as biotechnology, enzymology, green chemistry, genomics, immunology, materials science, neglected diseases and orphan drugs, pharmacogenomics, proteomics and toxicology.