One-Pot Sequential Alkynylation and Cycloaddition: Regioselective Construction and Biological Evaluation of Novel Benzoxazole–Triazole Derivatives

Individually, benzoxazole and triazole moieties are of significant biological interest owing to their importance in drugs and pharmaceuticals. To assess their combined biological impact when woven into one molecule, we designed a novel, regioselective, multicomponent, one-pot (MCOP) approach for the construction of benzoxazole-linked triazoles. The synthesis has been achieved in two sequential steps involving copper-catalyzed alkynylation of benzoxazole followed by a 1,3-dipolar cycloaddition reaction. By combination of these two bioactive units into one core, a series of new benzoxazole-triazole scaffolds has been synthesized and subjected to in vitro antibacterial and anticancer evaluation. Tests against clinical isolates of <i>Staphylococcus aureus</i> and <i>Escherichia coli</i> showed potent Gram-negative activity for compounds <b>4</b>{<i>1,1,1</i>}, <b>4</b>{<i>1,1,4</i>}, and <b>4</b>{<i>1,2,1</i>}. The cytotoxicity of the synthesized library was determined against three cancer cell lines: HeLa, SKBr3, and Hep G2. Compound <b>4</b>{<i>2,2,2</i>} showed significant cytotoxicity against all the cell lines. These preliminary bioassay evaluations strongly suggest the promise and scope of these novel molecules as therapeutic agents in medical science