ABSTRACT
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 acidswere 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 andin silico antioxidant and antimicrobial studies were carried out.Results:Compounds 1b and 1d displayed thebest in vitro antibacterial activities againstEscherichia coli, Salmonella typhi, Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and antifungal activities against Candida albicansandAspergillus niger. Compound 1f (IC50= 1.150±0.003μg/ml) exhibited the best in vitro antioxidant activity. Compound 1a had a higherin silicoantibacterial (-11.51 kcal/mol) binding energies than antibacterial reference drug, penicillin (-10.89 kcal/mol). Compound 1c had the highest in silicoantifungal binding energy (-10.48kcal/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.