虚拟查表明P2X7受体的潜在抑制剂
Murilo L Bello1, Guilherme Eduardo M Mendes2, Ana Cláudia R Silva3
1Pharmaceutical Planning and Computer Simulation Laboratory, Universidade Federal Do Rio de Janeiro, Rio de Janeiro, Brazil.
Computers in biology and medicine
|August 8, 2023
概括
研究人员对2774个分子进行了选,针对小鼠P2X7蛋白的抗炎潜力. 几种黄类药物和现有药物表现出抑制活性,验证了天然化合物和药物用于炎症治疗的重新用途.
科学领域:
- 药理学和药物发现
- 计算化学的计算化学
- 免疫学 免疫学 免疫学
背景情况:
- 由于复杂的治疗,长时间和高成本,炎症性疾病给公共卫生带来了重大挑战.
- 新型抗炎药物的开发至关重要,利用合成和天然化合物.
- 自然产品提供了大量的化学多样性,用于发现新的候选药物,而合成药物可以重新使用.
研究的目的:
- 通过虚拟查识别潜在的针对小鼠P2X7蛋白的抗炎化合物.
- 通过体外研究来验证已识别的化合物的抑制活性.
- 通过分子动力学分析强效抑制剂与P2X7受体的结合相互作用.
主要方法:
- 虚拟选2774个分子与小鼠P2X7蛋白进行对比.
- 在实验室中证实了小鼠细胞中P2X7受体抑制.
- 分子动力学模拟用于分析顶级抑制剂的蛋白质-配体相互作用.
主要成果:
- 虚拟查确定了五种黄类药物 (纳里鲁丁,迪奥斯,康普拉纳图赛德,赫斯佩里丁,奥洛辛B) 和药物 (韦尔帕塔斯维尔,伊塔西提尼布,利菲特格拉斯特) 作为潜在的P2X7配体.
- 试验室研究证实了这些配体对P2X7受体的抑制作用.
- 分子动力学模拟表明,韦尔帕塔斯维尔,伊塔西提尼布,石酸和纳里鲁丁仍然与P2X7受体的活性部位结合.
结论:
- 虚拟查和体外测试对于识别针对P2X7受体的新型抗炎药物是有效的.
- 黄类药物和现有的药物显示出对P2X7介导的炎症治疗的潜力.
- 这项研究强调了天然产品和药物重用在抗炎药物发现中的价值.
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