新型诺基诺与可能的抗菌活性在阴性耐药病原体:在的药物发现
Manuel Alejandro Coba-Males1, Martin J Lavecchia2, Christian David Alcívar-León3
1Grupo de Investigación en Biodiversidad, Zoonosis y Salud Pública (GIBCIZ), Instituto de Salud Pública y Zoonosis (CIZ), Facultad de Ciencias Químicas (FCQ), Universidad Central del Ecuador, Quito 170521, Ecuador.
Molecules (Basel, Switzerland)
|October 14, 2023
概括
新的诺基诺化合物显示出作为抗菌剂对抗耐药格兰氏阴性细菌的承诺. 化合物9FQ对DNA回旋酶表现出最强的结合亲和力,这表明有可能开发新型抗生素.
科学领域:
- 药用化学 医学化学
- 计算生物学 计算生物学
- 抗微生物耐药性 抗微生物耐药性
背景情况:
- 抗生素耐药性对全球健康构成重大挑战,需要开发新型抗菌剂.
- 世界卫生组织已经确定了几种格拉姆阴性病原体作为新疗法的首要目标.
研究的目的:
- 评估九种新型诺基诺化合物的潜在抗菌活性,以对抗关键耐药的阴性细菌.
- 研究这些化合物的与DNA回旋酶的结合相互作用,这是抗菌药物的关键目标.
主要方法:
- 采用了in silico分子对接和分子动力学 (MD) 模拟.
- 来自目标病原体的野生型 (WT) 和突变型 (MT) DNA 旋转酶作为生物目标.
- 分析了结合能量和与醇抗性决定区域 (QRDR) 的相互作用.
主要成果:
- 化合物9FQ在对接和MD模拟中表现出与大肠杆菌DNA旋转酶结合的最高结合能.
- 化合物9FQ与GyrA和GyrB中的关键QRDR残留物相互作用,可能抑制DNA复制.
- 化合物1FQ还对DNA回旋酶表现出有利的结合亲和力.
结论:
- 新型诺基诺化合物,特别是9FQ,显示出作为抗菌剂对抗阴性病原体的显著潜力.
- 这些in silico发现为进一步的体外验证和新抗生素的开发提供了坚实的基础.
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