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, <b>6k, 6f,</b> and <b>6b</b> 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 <b>6e</b> exhibited potent antibacterial activity (MIC = 0.5–2 μg/mL) against all tested strains, including <i>S. aureus</i>, <i>S. pyogenes</i>, <i>S. typhi</i>, and <i>P. aeruginosa</i>, comparable to streptomycin, while <b>6k</b> also showed notable inhibition (MIC = 2–4 μg/mL). In antioxidant assays, <b>6a</b> and <b>6j</b> 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 <b>6a</b> and <b>6j</b> (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 &gt;120 μg/mL for Vero cells, significantly higher than cisplatin (35.15 μg/mL). Molecular docking supported the <i>in vitro</i> 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.