Molecular Docking, QSAR and Microscopic Studies of Anti-trypanosomal Compounds from the Pathogen Box

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 inhibi-tion 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 com-pounds 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.

Automated summary

This study identified new anti-trypanosomal compounds targeting PGK and GAPDH, with key factors such as interacting charge surface and atomic mass affecting the inhibition effects. Additionally, potential novel anti-trypanosomal compounds were discovered from the pathogen box, with optimized pharmacological profiles for improving target specificity.