Synthesis, antimycobacterial evaluation, and molecular docking study of 1,2,4-triazole derivatives

Fifteen 1,2,4-triazole derivatives were synthesised in this study and their MIC values against Mycobacterium tuberculosis (Mtb) ranged from 2 to 32 & mu;g/mL. Furthermore, their antimycobacterial activity was positively correlated with the KatG enzyme docking score. Among the 15 compounds, compound 4 showed the strongest bactericidal activity with an MIC of 2 & mu;g/mL. The selectivity index of compound 4 is more than 10, indicating that the compound has low toxicity to animal cells and has the potential to become a drug. Molecular docking indicates that compound 4 can bind firmly to the Mtb KatG active site. The experimental results showed that compound 4 inhibited Mtb KatG and caused the accumulation of ROS in Mtb cells. We speculate that compound 4 causes the accumulation of ROS by inhibiting KatG, and ROS produces oxidative destruction, leading to the death of Mtb. This study provides a new idea for the development of novel anti-Mtb drugs.

Automated summary

In this study, fifteen 1,2,4-triazole derivatives were synthesized and evaluated for their MIC values against Mycobacterium tuberculosis (Mtb), ranging from 2 to 32 μg/mL. The antimycobacterial activity of these compounds was found to be positively correlated with the KatG enzyme docking score. Compound 4 exhibited the strongest bactericidal activity with an MIC of 2 μg/mL. It also showed low toxicity to animal cells and the ability to bind firmly to the Mtb KatG active site. The study suggests that compound 4 inhibits KatG, leading to the accumulation of ROS and oxidative destruction, ultimately causing the death of Mtb.