Design, Synthesis, Antimicrobial and Antioxidant Activities of Novel Threonine-based Sulfonamide Derivatives

Aim: To systematically design, synthesize and evaluate the biological activities of new threonine-based sulfonamide derivatives in order to achieve improved drug potency.

Methodology: Sulfamoyl carboxylic acids were prepared by the reaction of threonine with the appropriate sulfonyl chloride while their acetylated, carboxamide and aniline derivatives were synthesized via Lumiere-Barbier acetylation, Schotten-Baumann ammonolysis and Buchwald-Hartwig cross-coupling methods respectively. The FTIR, 1H-NMR, 13C-NMR and elemental analytical data were employed in the structural characterization. In vitro and in silico antioxidant and antimicrobial studies were carried out.

Results: Compounds 1b and 1d displayed the best in vitro antibacterial activities against Escherichia coli, Salmonella typhi, Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and antifungal activities against Candida albican sand Aspergillus niger. Compound 1f (IC50 = 1.150±0.003 µg/ml) exhibited the best in vitro antioxidant activity. Compound 1a had a higherin silico antibacterial (-11.51 kcal/mol) binding energies than antibacterial reference drug, penicillin (-10.89 kcal/mol). Compound 1c had the highest in silico antifungal binding energy (-10.48 kcal/mol)comparable to ketoconazole (-10.85 kcal/mol).

Conclusion: All the compounds were found to be potential antioxidant and antimicrobial drug candidates having complied with Lipinski’s rule of five.