合成及生物评价 4-取代苯乙烯基香豆素衍生物作为 TNF-α 和 IL-6 的抑制剂及其抗结核活性。
Synthesis and biological evaluation of 4-styrylcoumarin derivatives as inhibitors of TNF-α and IL-6 with anti-tubercular activity.
机构信息
R&D Centre, Torrent Research Centre, Ahmedabad 380 009, Gujarat, India.
出版信息
Bioorg Med Chem Lett. 2011 Apr 15;21(8):2547-9. doi: 10.1016/j.bmcl.2011.02.016. Epub 2011 Feb 15.
A series of 4-styrylcoumarin have been synthesized by Knoevenagel condensation between substituted 4-methylcoumarin-3-carbonitrile and different heterocyclic or aromatic aldehydes. 4-Methylcoumarin-3-carbonitrile has been synthesized by the base catalyzed reaction between substituted 2-hydroxyacetophenone and ethyl cyanoacetate. The structures of the newly synthesized compounds were confirmed by (1)H NMR, IR and mass spectral analysis. All the compounds were evaluated for their anti-inflammatory activity (against TNF-α and IL-6) and anti-tubercular activity. Compounds 6a, 6h and 6j exhibited promising activity against IL-6 with 72-87% inhibition and compound 6v showed potent activity against TNF-α with 73% inhibition at 10 μM concentration. Whereas compounds 6n, 6o, 6r and 6u showed very good anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain at <6.25 μM.
通过取代的 4-甲基香豆素-3-腈与不同杂环或芳醛之间的 Knoevenagel 缩合反应，合成了一系列 4-苯乙烯基香豆素。4-甲基香豆素-3-腈是通过取代的 2-羟基苯乙酮与氰基乙酸乙酯在碱性条件下催化反应合成的。新合成化合物的结构通过 1H NMR、IR 和质谱分析得到确认。所有化合物均进行了抗炎活性（针对 TNF-α 和 IL-6）和抗结核活性评估。化合物 6a、6h 和 6j 对 IL-6 的抑制活性达到 72-87%，化合物 6v 在 10 μM 浓度下对 TNF-α 的抑制活性达到 73%，具有良好的活性。而化合物 6n、6o、6r 和 6u 在 <6.25 μM 时对结核分枝杆菌 H37Rv 株表现出非常好的抗结核活性。
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