一项全面的计算研究,以探索有前途的天然生物活性化合物,针对大肠杆菌中的葡萄糖转移酶MurG,以潜在的药物开发
Amneh Shtaiwi1, Shafi Ullah Khan2,3, Meriem Khedraoui4
1Faculty of Pharmacy, Middle East University, Queen Alia Airport Street, Amman, P.O. Box No. 11610, Jordan. ashtaiwi@meu.edu.jo.
Scientific reports
|March 27, 2024
概括
这项研究确定了潜在的天然产品抑制剂,向大肠杆菌中的MurG酶. NPC272174显示出高稳定性,为针对耐药菌株的新型抗菌药物发现提供了有希望的途径.
科学领域:
- 生物化学 生物化学
- 微生物学 微生物学
- 药物发现 药物发现 药物发现
背景情况:
- 二醇糖的生物合成对细菌细胞完整性至关重要.
- 糖系转移酶MurG是一种关键酶,也是抗生素的点.
- 现有的MurG抑制剂面临诸如大肠杆菌中毒性和耐药性等挑战.
研究的目的:
- 确定新型天然产品 (NP) 作为埃舍里希亚大肠杆菌中MurG的潜在抑制剂.
- 克服目前MurG抑制剂的局限性,包括毒性和耐药性.
主要方法:
- 从NPASS数据库中使用分子对接对30,926个NP进行虚拟选.
- 在药物相似性,ADMET特性和药理动力学测试的形评估.
- 分子动力学 (MD) 模拟高达400 ns和对顶级候选者的绑定能量计算.
主要成果:
- 20个NP通过了初始功效,药理动力学和ADMET查.
- 分子对接验证了所选化合物.
- MD模拟表明天然产品NPC272174与MurG.复合的高稳定性.
结论:
- 天然产品NPC272174显示出作为MurG抑制剂的显著稳定性.
- 这项研究提出了有前途的天然产品候选人,用于开发新的抗菌剂对抗大肠杆菌.
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