Background: Trypanosoma brucei (T. brucei) is the cause of the deadly human African trypanosomiasis (HAT) with a case fatality ratio of 10%.

Objective: Targeting the essential Trypanosomal glucose metabolism pathway through the inhibition of phosphoglycerate kinase (PGK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a valid strategy for anti-T. brucei drug development.

Methods: Here, quantitative structure activity relationship, molecular docking and microscopic studies were used to describe the mode of inhibition of selected compounds from the pathogen box PGK and GAPDH.

Results: We identified 4 hit compounds from the pathogen box with optimal binding and chemical interactions. Notably, it was identified that interacting charge surface and atomic mass were key aspects of both PGK and GAPDH inhibition. Also, novel anti-trypanosomal compounds were identified from the pathogen box and their half maximal inhibitory concentrations were described.

Conclusion: Our study presents new anti-trypanosomal compounds with optimal pharmacological profiles and an optimization strategy for improving target specificity in the rational design of novel anti-trypanosomal compounds.

背景：布氏锥虫 (T. brucei) 是致命的非洲人类锥虫病 (HAT) 的病因，病死率为 10%。

目的：通过抑制磷酸甘油酸激酶 (PGK) 和 3-磷酸甘油醛脱氢酶 (GAPDH) 来靶向必需的锥虫葡萄糖代谢途径是抗 T 的有效策略。布鲁氏药物开发。

方法：在这里，定量的构效关系、分子对接和显微镜研究被用来描述来自病原体盒 PGK 和 GAPDH 的选定化合物的抑制模式。

结果：我们从病原体盒中鉴定出 4 种具有最佳结合和化学相互作用的命中化合物。值得注意的是，已确定相互作用的电荷表面和原子质量是 PGK 和 GAPDH 抑制的关键方面。此外，从病原体盒中鉴定了新的抗锥虫化合物，并描述了它们的半数最大抑制浓度。

结论：我们的研究提出了具有最佳药理学特征的新型抗锥虫化合物，以及在新型抗锥虫化合物的合理设计中提高靶标特异性的优化策略。