针对点击衍生异酸-二氧化碳-1,2,3-三醇的抗菌,抗菌膜,对接,DFT和分子动力学研究
Aman Kumar1, Kashmiri Lal1, Mohd Murtaza2
1Department of Chemistry, Guru Jambheshwar University of Science & Technology, Hisar, Haryana, India.
Journal of biomolecular structure & dynamics
|September 11, 2023
概括
合成了新型的伊萨-提奥西米卡巴-1,2,3-二醇混合物,显示出强大的抗微生物和抗菌膜活性. 化合物8d对大肠杆菌和黄金杆菌具有显著的疗效,突出了它们作为新治疗剂的潜力.
科学领域:
- 药用化学 医学化学
- 有机合成 有机合成
- 微生物学 微生物学
背景情况:
- 抗微生物耐药性需要开发新的治疗药物.
- 伊萨丁 - 提奥西米卡巴基架以其多样化的生物活动而闻名.
- 1,2,3-二醇部分可以增强药理性质.
研究的目的:
- 设计和合成新型的伊萨-西西米卡巴-1,2,3-二醇混合物.
- 评估这些化合物的抗微生物和抗菌膜潜力.
- 研究结构-活动关系和分子相互作用.
主要方法:
- 通过铜(I) 催化基-化循环添加 (CuAAC) 合成混合化合物.
- 使用FTIR,NMR (1H,13C,2D) 和HRMS进行表征.
- 针对各种微生物物种的抗微生物和抗菌膜测定.
- 分子对接,DFT计算和分子动力学模拟.
主要成果:
- 成功合成和表征了新型的伊萨-提奥西米卡巴-1,2,3-醇杂交物.
- 化合物8d对大肠杆菌和黄金色杆菌具有强烈的抗菌活性 (MIC = 0.0067 μmol/mL).
- 化合物8b,8c,8d,8e,9a和10显著抑制了生物膜的形成.
结论:
- 合成的伊萨-提奥西米卡巴-1,2,3-醇代表了一类有前途的抗微生物和抗菌膜剂.
- 化合物8d是进一步开发抗细菌感染的主要候选物.
- 分子建模研究为结合机制提供了洞察力,并支持观察到的生物活动.
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