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小说皇冠以太功能化基酸丁乙醇:合成,生物评估,在ADMET,和分子对接研究
Hira Sultan1, Nuzhat Arshad1, Mehreen Lateef2
1Department of Chemistry, NED University of Engineering and Technology, Karachi 75270, Pakistan.
新型冠状乙烯与基酸丁烯结合,合成并测试了药理活动. 两个化合物FABE-16-crown-4和FABE-19-crown-5显示出显著的抗氧化潜力和有利的药物相似性.
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:
- 皇冠乙烯因其离子体特性而闻名,类似于瓦利诺米辛等天然化合物.
- 持续需要开发新的药理活性分子.
- 酸衍生物为新药开发提供了支架.
研究的目的:
- 合成和表征一种新型系列的皇冠乙烯,与Fusidic酸丁烯结合.
- 评估合成化合物的体外抗氧化和α-葡萄糖酶抑制活性.
- 通过分子对接来研究结合相互作用,并预测它们的药物相似性.
主要方法:
- 使用NMR,FT-IR和质谱学合成和对皇冠衍生物的结构性表征.
- 在体外抗氧化活性测定与丁酸素 (BHA) 相比.
- 与acarbose相比,体外α-葡萄糖酶抑制试验.
- 用人类抗氧化蛋白 (百氧化素5) 进行分子对接研究.
- 在 silico ADMET 预测药物相似性.
主要成果:
- 化合物FABE-16-crown-4 (10b) 和FABE-19-crown-5 (10c) 显示出强大的抗氧化活性 (IC50 = 分别为22.5 ± 0.2 μM和32.1 ± 0.3 μM),性能优于标准BHA.
- 分子对接揭示了10b (-6.7 kcal/mol) 和10c (-6.5 kcal/mol) 与过氧化素5.5的良好结合得分.
- 合成的皇冠乙烯表现出适度的α-葡萄糖酶抑制 (IC50 = 23.5 ± 0.2至76.5 ± 0.1μM).
- 在基ADMET预测表明,这些化合物遵守利宾斯基的5规则 (bRO5) 和维伯规则,这表明口服生物可用性良好.
结论:
- 新的皇冠乙醇-基酸布틸结合物具有显著的抗氧化特性.
- 这些化合物显示出作为治疗剂的潜力,特别是在涉及氧化应激的条件下.
- 在中有利的ADMET概况支持它们进一步发展为口服药物.
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