Synthesis, biological evaluation and molecular docking studies of new hybrids of α-tocopherol and aryl/heterocyclic group through 1,2,3-triazole spacer

A new series of hybrids of alpha-tocopherol and aryl/heterocyclic moieties through 1,2,3-triazole linker were made by rationally combining a biologically active alpha-tocopherol and substituted aromatic or heterocyclic moieties in single molecular frame using the click chemistry method. In a nutshell, the novel compounds (3a-h) were made by O-alkylating alpha-tocopherol, proceeded by copper (I)-catalyzed click reaction and the Huisgen [3 + 2] cycloaddition using various aromatic and heterocyclic azides (2a-h). By using 1H, 13C NMR, and mass spectroscopy techniques, all of the recently synthesized compounds were characterized and their antibacterial and antioxidant capabilities were assessed. Among the synthesized compounds, the most effective synthetic molecule against all bacterial strains was 3e with a naphthyl moiety, whereas 3d with a phenolic moiety showed potent antioxidant activity. To better understand the binding interactions, exploratory molecular docking investigation was conducted against the faBH enzyme of E. coli.