木姜子属N-烷基酰胺类化合物抑制HDAC8的虚拟筛选——基于药效团模型与分子对接技术

Screening of HDAC8 inhibitors of N-alkylamides in Litsea plants based on molecular docking and pharmacophore model

  • 摘要: 木姜子属植物(Litsea)具有丰富的药用价值,其中的N-烷基酰胺类物质除了具有抗炎活性外,还可能存在潜在的抗癌活性. 利用构建的药效团和分子对接的方法对17个木姜子属N-烷基酰胺类化合物进行了虚拟筛选,结果显示共有15个N-烷基酰胺类物质与药效团模型匹配,结合分子对接结果,共筛选出2个评价较好的N-烷基酰胺化合物,10号与11号在两次筛选结果上都具有较高的评价结果,二者与受体蛋白的结合方式与原配体和上市药物tubulin具有较高的相似性. 研究结果表明木姜子属N-烷基酰胺类化合物具有潜在的HDAC8抑制活性,参考本次的筛选结果,10号与11号N-烷基酰胺化合物具有潜在的研究价值,值得开展深入研究.

     

    Abstract: Litsea is abundant in various biomolecules, which contribute to its medicinal properties. N-alkylamides exhibited potential anticancer activities alongside their known anti-inflammatory effects. In this study, seventeen N-alkylamides derived from Litsea were subjected to virtual screening utilizing a constructed pharmacophore model and molecular docking techniques. The findings revealed that fifteen N-alkylamides corresponded with the pharmacophore model. Upon integrating, the molecular docking results, two N-alkylamides, specifically compounds No. 10 and No. 11, demonstrated superior evaluation outcomes in both screening methods. The binding interactions of these two compounds with receptor proteins exhibited a high degree of similarity to the original ligand and the commercially available drug tubulin. These results indicate that the N-alkylamides possess potential HDAC8 inhibitory activity, with compounds 10 and 11 showing significant promise and warranting further investigation.

     

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