2β-Acetoxyferruginol derivatives as α-glucosidase inhibitors: Synthesis and biological evaluation

IF 4.5 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic Chemistry Pub Date : 2024-08-29 DOI:10.1016/j.bioorg.2024.107770

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Abstract

To find potential α-glucosidase inhibitors, a series of 2β-acetoxyferuginol derivatives containing cinnamic acid (WXC-1 ∼ 25) were synthesized and investigated their biological activity. All derivatives (WXC-1 ∼ 25) displayed better inhibitory activity (IC₅₀ values: 7.56 ± 1.35 ∼ 25.63 ± 1.72 μM) compared to acarbose (IC₅₀ vaule: 564.28 ± 48.68 μM). In particularly, WXC-25 with 4-hydroxycinnamic acid section showed the best inhibitory activity (IC₅₀ vaule: 2.02 ± 0.14 μM), ∼75-fold stronger than acarbose. Kinetics results suggested WXC-25 being one reversible non-competition inhibitors. Fluorescence quenching results indicated that WXC-25 quenched the fluorescence of α-glucosidase in a static manner. 3D fluorescence spectra results indicated that WXC-25 treatment could cause the conformation changes of α-glucosidase. Moreover, molecular docking simulated the detailed interaction of WXC25 with α-glucosidase.

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作为α-葡萄糖苷酶抑制剂的 2β-Acetoxyferruginol 衍生物：合成与生物学评价

为了寻找潜在的α-葡萄糖苷酶抑制剂，研究人员合成了一系列含有肉桂酸的 2β-acetoxyferuginol 衍生物（WXC-1 ∼ 25），并对其生物活性进行了研究。与阿卡波糖（IC50 值：564.28 ± 48.68 μM）相比，所有衍生物（WXC-1 ∼ 25）都显示出更好的抑制活性（IC50 值：7.56 ± 1.35 ∼ 25.63 ± 1.72 μM）。特别是含有 4-羟基肉桂酸部分的 WXC-25 显示出最佳的抑制活性（IC50 vaule：2.02 ± 0.14 μM），比阿卡波糖强 75 倍。动力学结果表明，WXC-25 是一种可逆的非竞争抑制剂。荧光淬灭结果表明，WXC-25 以静态方式淬灭了α-葡萄糖苷酶的荧光。三维荧光光谱结果表明，WXC-25 可导致α-葡萄糖苷酶的构象发生变化。此外，分子对接模拟了WXC25与α-葡萄糖苷酶的详细相互作用。

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来源期刊

Bioorganic Chemistry 生物-生化与分子生物学

CiteScore

9.70

自引率

3.90%

发文量

679

审稿时长

31 days

期刊介绍： Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry. For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature. The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.