Design, Synthesis, and In Vitro Evaluation of 4-(Arylchalcogenyl)methyl)-1H-1,2,3-triazol-1-yl-menadione: Exploring Their Potential Against Tuberculosis.

Background/

Objectives

In this study, a novel series of 4-(arylchalcogenyl)methyl)-1H-1,2,3-Triazol-1-yl-menadione derivatives were synthesized to explore their potential as new antituberculosis (anti-TB) agents. Selenium-containing compounds are known for their significant antimycobacterial activity, which motivated their inclusion in the design.

Methods

The target compounds were synthesized via a copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, affording yields ranging from 34% to 93%. All compounds were evaluated in vitro for anti-TB activity against Mycobacterium tuberculosis H37Rv (ATCC 27294), as well as a drug-resistant strain (T113/09).

Results

Several selenium-containing derivatives exhibited promising activity. Compounds 9b and 9g were equipotent to the first-line anti-TB drug, and one compound surpassed its activity. Notably, compounds 9a, 9b, 9g, and 9h also showed efficacy against the INH- and RIF-resistant Mtb strain T113/09.

Conclusions

The efficacy of selenium-containing triazole-menadione hybrids against both sensitive and resistant Mtb strains highlight their potential as candidates for addressing antimicrobial resistance in TB treatment. Further investigations are required to understand their mechanisms of action and assess their in vivo therapeutic potential..