A Click Chemistry Approach for the Synthesis of Triazole Linked Vanillin Scaffolds as Potent Pharmacophores: Anti-Diabetic, Anti-Inflammatory, Antioxidant, Molecular Docking and ADMET Investigations

In this study a series of triazole linked vanillin derivatives were synthesized via Click chemistry and characterized using FTIR,1H NMR,1³C NMR, and HRMS/MS. Among the synthesized compounds, 6k, 6f, and 6b showed strong α-amylase inhibitory activity (IC50 = 50.70, 51.36, and 53.25 μg/mL, respectively) and α-glucosidase inhibitory activity (IC50 = 36.85, 37.99, and 38.49 μg/mL), comparable to acarbose (IC50 = 54.38 and 39.04 μg/mL). Compound 6e exhibited potent antibacterial activity (MIC = 0.5–2 μg/mL) against all tested strains, including S. aureus, S. pyogenes, S. typhi, and P. aeruginosa, comparable to streptomycin, while 6k also showed notable inhibition (MIC = 2–4 μg/mL). In antioxidant assays, 6a and 6j demonstrated IC50 values (48.25 and 49.31 μg/mL) comparable to ascorbic acid (IC50 = 49.18 μg/mL). Anti-inflammatory activity was significant for 6a and 6j (IC50 = 36.66 and 37.21 μg/mL), surpassing diclofenac (IC50 = 37.89 μg/mL). The compounds were nontoxic in cytotoxicity studies, with IC50 values >120 μg/mL for Vero cells, significantly higher than cisplatin (35.15 μg/mL). Molecular docking supported the in vitro results, with active compounds showing strong binding affinities, and SwissADME analysis indicated favorable pharmacokinetic properties. These findings highlight the multifunctional therapeutic potential of the designed compounds as anti-diabetic, antibacterial, antioxidant, and anti-inflammatory agents.