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

<b>Background/Objectives:</b> 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. <b>Methods:</b> 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 <i>Mycobacterium tuberculosis</i> H37Rv (ATCC 27294), as well as a drug-resistant strain (T113/09). <b>Results:</b> Several selenium-containing derivatives exhibited promising activity. Compounds <b>9b</b> and <b>9g</b> were equipotent to the first-line anti-TB drug, and one compound surpassed its activity. Notably, compounds <b>9a</b>, <b>9b</b>, <b>9g</b>, and <b>9h</b> also showed efficacy against the INH- and RIF-resistant <i>Mtb</i> strain T113/09. <b>Conclusions:</b> The efficacy of selenium-containing triazole-menadione hybrids against both sensitive and resistant <i>Mtb</i> 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..