使用计算和结构导向方法发现大肠杆菌排泄融合蛋白的向抑制剂
Shweta Singh Chauhan1,2, Anshika Gupta1, Aashna Srivastava1
1Computational Toxicology Facility, Toxicoinformatics & Industrial Research, CSIR-Indian Institute of Toxicology Research, Lucknow, India.
Journal of computational chemistry
|September 1, 2023
概括
这项研究确定了抑制细菌排泄的新化合物,这是多药耐药性的关键机制. 这些发现为恢复抗生素对抗耐药性病原体的有效性提供了一个有希望的策略.
科学领域:
- 微生物学 微生物学
- 药理学 药理学是指药理学的学科.
- 计算化学计算化学
背景情况:
- 细菌病原体的多药性耐药性 (MDR) 构成了重大的临床挑战,治疗选择有限.
- 排泄是细菌耐药性的一个主要机制,积极将抗生素从细胞中驱逐出来.
- 抑制这些排泄是一种恢复抗生素疗效的有希望的策略.
研究的目的:
- 识别和计算评估大肠杆菌AcrB-AcrA排泄系统的抑制剂.
- 探索已知抑制剂的潜在化学衍生物,以提高对抗多药耐药细菌的疗效.
主要方法:
- 文献挖掘以选择现有的AcrB-AcrA.Acr抑制剂.
- 虚拟选,分子对接和密度函数理论 (DFT) 计算来评估抑制潜力.
- 对新型衍生品的评估与野生型和突变的排泄子单元相比.
主要成果:
- 化合物2 (ZINC000072136376) 显示出显著的抑制作用和强大的结合AcrA.
- 化合物3 (ZINC000072266819) 对非突变和突变的AcrB子单元表现出强大的抑制和强大的结合.
- 已识别的衍生品显示出改善抑制活性的潜力.
结论:
- 该研究确定了具有有前途的抑制作用于大肠杆菌排泄系统关键组件的特定化合物.
- 这些发现表明,通过向排泄来克服抗生素耐药性的潜在治疗策略.
- 这些衍生品的进一步开发可能会导致针对多药耐药性感染的新疗法.
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