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探索自然产品图谱 (NPAtlas) 数据库,寻找具有抗结核活性的潜在不可逆转共价DprE1抑制剂:一种集成的体方法

Mahmoud A A Ibrahim^1,2,3, Doaa G M Mahmoud¹, Sherif S Ebada^4,5

¹Chemistry Department, Faculty of Science, Minia University, Minia, 61519, Egypt, minia.edu.eg.

Journal of tropical medicine

|February 16, 2026

概括

结核病 (TB) 是一个主要的全球健康威胁,特别是耐药菌株. 这项研究确定了含有的新型天然产品,作为潜在的脱烯-D-ribose氧化酶 (DprE1) 的共价抑制剂,这是新的抗结核药物的关键标.

科学领域:

生物化学和分子生物学
药用化学医学化学
计算机化药物发现技术

背景情况:

结核病 (TB) 仍然是全球领先的传染病杀手,多抗药性 (MDR-TB) 和广泛抗药性 (XDR-TB) 菌株的增加需要新的治疗策略.
抑制decapenylphosphoryl-D-ribose氧化酶 (DprE1),对于菌根菌细胞壁生物合成至关重要,为开发新的抗结核治疗方法提供了一个有希望的途径.

研究的目的:

从NPAtlas数据库中识别和优先考虑天然产品作为使用in silico方法的DprE1潜在的共价抑制剂.
选含有酸盐的天然产品以检查它们抑制DprE1的能力,解决对抗耐药菌株的新抗结核病治疗药物的迫切需要.

主要方法:

对来自NPAtlas数据库的133种含化合物进行了对DprE1目标进行共价对接模拟.
具有有利的对接分数的化合物经历了分子动力学模拟 (MDS) 和使用MM-GBSA方法的结合能量的计算.
预测了物理化学性质和ADMET (吸收,分布,新陈代谢,分泌和毒性) 概况,以评估潜在的药物相似性.

主要成果:

六种NPAtlas化合物 (NPA011203,NPA013234,NPA016048,NPA012944,NPA001712,NPA002823) 与参考化合物PBTZ169相比,对DprE1具有更高的结合亲和力,计算的结合自由能量 (ΔGbinding) 在-50.7至-75.6 kcal·mol-1.1之间.
这些已识别的化合物在MDS的250 ns内在DprE1活性位点内表现出稳定的相互作用.
在的预测表明了有利的物理化学特性,良好的吸收潜力和低毒性,表明可能的口服生物可用性.

结论:

该研究成功地确定了几种有前途的天然产品衍生化合物作为潜在的共价DprE1抑制剂.
这些化合物代表了作为新型抗结核病剂的进一步体外和体内研究的可行候选者.
这些发现为开发抗药性结核病的新治疗策略提供了坚实的基础.

关键词:

DprE1E1 的意思是什么?在 NPAtlas 中.具有约束力的能源计算.同价对接对接是共价对接.分子动力学模拟模拟

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