Integrated Study of Novel Triazole-Linked Schiff Bases: From Efficient Synthesis and Structural Elucidation to Antimicrobial Activity, DFT, and Molecular Docking

Introduction:
Triazole-based Schiff bases and their metal complexes have attracted considerable attention due to their potential as therapeutic agents with antimicrobial and anti-inflammatory activities. The present study focuses on the synthesis, characterization, and biological evaluation of novel triazole-linked Schiff bases and their Co(II), Ni(II), and Cu(II) complexes.

Methods:
Two Schiff base ligands (L1 and L2) and their complexes (3–10) were synthesized and structurally characterized. Antimicrobial activity was assessed in vitro against Gram-positive and Gram-negative bacteria (Staphylococcus aureus, Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli) and fungal strains (Candida albicans and Cryptococcus neoformans). Growth inhibition was quantified spectrophotometrically (OD600 for bacteria, OD530 for C. albicans, and OD600–570 following resazurin reduction for C. neoformans). Anti-inflammatory activity was evaluated using the protein denaturation inhibition assay. Computational studies included density functional theory (DFT), molecular electrostatic potential (MESP) mapping, ADMET predictions, and molecular docking targeting enoyl-acyl carrier protein reductase (Mycobacterium tuberculosis, PDB ID: 6H53) and cyclooxygenase-2 (COX-2, PDB ID: 1CX2).

Results:
Ligand L1 displayed remarkable anti-TB potency (MIC: 0.007 ± 0.002 µmol/mL), surpassing streptomycin. Among the synthesized complexes, compound (10) was the most potent, showing strong antibacterial and antifungal effects (MIC: 0.0066 µmol/mL) and the highest anti-inflammatory activity (IC₅₀ = 6.75 ± 0.09 µM). Docking results supported the experimental findings, with favorable binding energies for both 6H53 and COX-2.

Conclusions:
This integrated experimental and in silico investigation demonstrates that triazole-linked Schiff bases and their metal complexes, particularly complex (10), exhibit significant antimicrobial and anti-inflammatory potential. These findings highlight their promise as lead compounds for the development of future therapeutic agents.