Synthesis, Characterization, and Molecular Docking Studies of Some Novel Amino acid-Sulfapyridine Hybrids as Potential Antimicrobial Agents

Abstract

The first antimicrobial medications discovered to be effective against pyogenic bacterial infections
were sulfa drugs. Sulfapyridine, a versatile synthetic precursor, was used to synthesize new amino acid sulfonamide
hybrids. The elemental and spectral data of the newly synthesized compounds (5a-d) supported their structures.
The synthesized compounds (5a-d) were tested for antibacterial activities against Bacillus subtilis, Staphylococcus
aureus, Pseudomonas aeruginosa, and Escherichia coli, as well as antifungal activities against Aspergillus niger,
and Candida albicans, and were compared to the reference drugs gentamycin and miconazole for antibacterial and
antifungal activity, respectively. Some of the newly synthesized compounds (5c and 5d) showed potential antimicrobial activities against a variety of strains, suggesting that they could be a good candidate. To explore favorable
binding interactions, molecular docking studies were carried out using the target dihydrofolate reductase (DHFR)
enzyme (PDB ID: 3SRQ) from a S. aureus strain for all of these newly synthesized compounds. The results of
docking studies clearly showed that all compounds fit nicely into the active site and form hydrogen bonds, van der
Waals, π-σ, and π-alkyl interactions with the active site residues. The binding free energy of 5a (-6.9 kcal/mol), 5b
(-7.1 kcal/mol), 5c (-7.2 kcal/mol), and 5d (-7.4 kcal/mol) indicate sufficient affinity between the sulfonamides and
the enzyme. Among these compounds, 5d emerged as the most potent DHFR inhibitor