purin-5-N-isosteresas抗炎剂的合成,对接和生物评估
Ahmed M El-Saghier1, Souhaila S Enaili1,2, Aly Abdou1
1Chemistry Department, Faculty of Science, Sohag University 282524 Sohag Egypt el.saghier@science.sohag.edu.eg.
RSC advances
|June 4, 2024
概括
新合成的特里亚-特里亚衍生物通过抑制循环氧化酶 (COX) 酶表现出强大的抗炎作用. 这些化合物表现出与印米他辛相比更高的疗效,这表明有可能开发新的抗炎药物.
科学领域:
- 药用化学 医学化学
- 有机合成 有机合成
- 药理学 药理学是指药理学的学科.
背景情况:
- 炎症是一种复杂的生物反应,与各种疾病有关.
- 非类固醇抗炎药物 (NSAIDs) 广泛使用,但可能会产生副作用.
- 开发具有更好的疗效和安全性特征的新型抗炎药物至关重要.
研究的目的:
- 为了合成新型的5-amino-7- ((替代) -N- ((4-sulfamoylphenyl) -4,7-dihydro-[1,2,4]-triazole[1,5-a][1,3,5]triazine-2-carboxamide衍生物.
- 为了评估这些合成化合物的体外抗炎活性.
- 研究这些化合物作为循环氧化酶 (COX) 酶抑制剂的潜力.
主要方法:
- 在绿色条件下,三醇-三氨酸衍生物的三组合合成.
- 在体外抗炎试验包括抑制白蛋白变性,红细胞血解和COX抑制.
- 用COX-2合成的化合物的分子对接研究 (PDB ID: 5IKT).
- 密度功能理论 (DFT) 对排名第一的化合物的分析.
主要成果:
- 所有合成的化合物在体外表现出显著的抗炎活性.
- 化合物显示,与印梅他辛相比,对白蛋白变性,红细胞血解和COX酶的抑制能力更强.
- 对于COX-1的IC50值在40.04-87.29微克/毫升之间,而对于COX-2则在27.76-42.3微克/毫升之间.
- 分子对接揭示了与COX-2的化合物4,11和12的高结合亲和力.
- 对强效化合物的DFT分析表明,与印米相比,强效化合物的HOMO-LUMO能量差异较小.
结论:
- 新型的triazole-triazine衍生物在体外具有显著的抗炎性质.
- 这些化合物有效地稳定红细胞膜,抑制蛋白质变性,并抑制COX酶.
- 化合物4,11和12显示出有前途的COX-2抑制能力,需要进一步调查针对COX-2的药物开发.
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