Substituted 1,3,5-Triazine Derivatives as Promising Antimicrobial Leads: Synthesis, Spectral Characterization and In Silico Investigation
Keywords:
1,3,5-Triazine, Antimicrobial activity, Molecular docking, SwissADME, Dihydrofolate reductase, DNA gyrase, Sulfonamide hybrids, Drug-likenessAbstract
A new series of substituted 1,3,5-triazine derivatives (4a–4f) was successfully synthesized through a two-step nucleophilic aromatic substitution strategy using cyanuric chloride as the key precursor. The synthesized compounds were characterized by melting point determination, TLC, IR, 1H NMR, LC-MS, and elemental analysis, which confirmed the proposed structures. The in vitro antimicrobial activity of the compounds was evaluated against selected Gram-positive bacteria (Staphylococcus aureus, Bacillus anthracis), Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli), and fungal strains (Candida albicans and Aspergillus niger) using the cup plate method. Among the tested derivatives, compounds 4c and 4d exhibited the most promising broad-spectrum antimicrobial activity, showing inhibition zones close to the standard drugs. In silico ADME studies using SwissADME indicated acceptable lipophilicity and hydrogen-bonding properties, although high TPSA and molecular weight may limit oral bioavailability. Molecular docking studies against Mycobacterium tuberculosis dihydrofolate reductase (PDB ID: 4KM2) and Staphylococcus aureus DNA gyrase (PDB ID: 2XCT) revealed favorable binding affinities for all synthesized compounds, with 4c showing the best docking performance against both targets. The combined synthetic, biological, and computational findings suggest that these triazine-based hybrids, particularly 4c and 4d, may serve as promising lead molecules for the development of new antimicrobial agents.
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