Design, Synthesis, Characterization, In silico Evaluation, and Antimicrobial Potential of Novel 1,3,5-Triazine-amino-benzenesulfonamide Derivatives: Part 2

Abstract

In continuation of our previous work, a series of 1,3,5-triazine–aminobenzenesulfonamide derivatives (A13-A25) was synthesized through sequential nucleophilic substitution reactions of cyanuric chloride and evaluated for their structural, antimicrobial and pharmacokinetic properties. The synthesized compounds were characterized by FTIR, ¹H NMR, ¹³C NMR and mass spectrometry. The spectral data supported the presence of the triazine, sulfonamide and substituted amino functionalities. The antimicrobial activity was assessed by the tube dilution method against selected Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus), Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and fungal strains (Candida albicans and Aspergillus niger) using trimethoprim as the reference drug. Molecular docking against dihydrofolate reductase was performed to examine the binding behaviour of the synthesized derivatives. The calculated binding affinities ranged from -8.5 to -10.2 kcal mol^–1, compared with -7.6 kcal mol^–1 for trimethoprim. Compound A23 showed the most favourable docking score (-10.2 kcal mol^–1), followed by A22 (-9.8 kcal mol^–1) and A24 (-9.7 kcal mol^–1). SwissADME-based analysis predicted favourable gastrointestinal absorption for several derivatives, particularly A19, A21 and A22, while most compounds showed limited BBB penetration. The ADMET profile revealed high plasma protein binding for most derivatives and variable CYP enzyme interactions.