Cyclodextrin‐Assisted Synthesis, Statistical Optimization, Antibacterial Evaluation, DFT, and Molecular Docking of Quinolone–1,2,3‐Triazole Hybrids

Abstract A series of quinoline–triazole hybrids was synthesized via Cu(I)‐catalyzed azide–alkyne cycloaddition between propargylated 2‐quinolones and alkyl or glycinate‐derived azides, under eco‐friendly conditions using CuSO 4 /cyclodextrin. Structures were confirmed by NMR and Mass spectromety ESI. DFT and Fukui analyses supported a polar [3 + 2] cycloaddition mechanism. Molecular docking showed strong binding of triazole derivatives (notably 4b and 4c ) to Streptococcus pneumoniae PBPs, with binding energies up to –8.15 kcal/mol. Design‐expert optimization confirmed optimal β‐CD and reaction time conditions. Antibacterial testing revealed that triazole derivatives exhibited enhanced activity (MICs as low as 0.31 µg/mL), especially against S. pneumoniae . These results highlight the potential of triazole‐functionalized quinolones as promising antimicrobial agents.