Synthesis, Characterisation, Molecular Docking and Antimicrobial Evaluation of Certain Cyclic Amine-Containing Trisubstituted 1,3,5-Triazine Derivatives

Abstract

A series of novel tri-substituted 1,3,5-triazine derivatives (5a-l) was synthesised and characterised using analytical and spectroscopic techniques including IR, ¹H NMR, ¹³C NMR and mass spectrometry. The antimicrobial efficacy of the synthesised compounds was evaluated against four bacterial strains (Escherichia coli MTCC 443, Pseudomonas aeruginosa MTCC 1688, Staphylococcus aureus MTCC 96 and Streptococcus pyogenes MTCC 442) and three fungal strains (Candida albicans MTCC 227, Aspergillus niger MTCC 282 and Aspergillus clavatus MTCC 1323). Compound 5i showed the lowest MIC against S. aureus (MIC 62.5 µg/mL), while compound 5b demonstrated moderate broad-spectrum antibacterial activity with MIC values of 50-100 µg/mL, representing the most active member of the series (MIC 50 µg/mL vs. ciprofloxacin MIC 25 µg/mL). Compound 5k showed significant antifungal activity against C. albicans (MIC 100 µg/mL), superior to griseofulvin for this specific strain (MIC 500 µg/mL). Molecular docking studies against S. aureus DNA gyrase (PDB: 3FY8) revealed that compound 5e exhibited the highest binding affinity among the synthesised compounds (docking score: -7.074 kcal/mol), lower than the reference ciprofloxacin (-7.778 kcal/mol). The compounds demonstrated interactions with key active-site residues via hydrophobic contacts, hydrogen bonding with TYR 98, halogen bonding and electrostatic interactions with ASP 27 and LYS 45, suggesting DNA gyrase as a possible target for further exploration. These findings indicate that 1,3,5-triazine scaffolds are promising leads for the development of antimicrobial agents targeting DNA gyrase.