Synthesis, Molecular Docking Study of Benzoylated Sulfonamide and Benzamide Conjugates of 7‐Chloroquinoline with Antioxidant and Antimicrobial Activity

Abstract

ABSTRACT A series of quinoline–sulfonamide–amino acid hybrids were designed and synthesized, and their antioxidant and antimicrobial properties were evaluated. 4,7‐Dichloroquinoline was efficiently converted to 7‐(chloroquinolin‐4‐yl)diaminoethane in high yield (97.46%). Condensation of phenylsulfonyl chloride with selected L‐amino acids afforded sulfonamide intermediates in 85.0–92.5% yields, which upon subsequent benzoylation produced benzoylated derivatives in good yields. Amidation of the benzoylated sulfonamides with 7‐(chloroquinolin‐4‐yl)diaminoethane yielded the target conjugates in moderate yields. The synthesized compounds were evaluated for antioxidant activity using the DPPH free radical scavenging assay and for antimicrobial activity using the minimum inhibitory concentration (MIC) method. Among the tested compounds, derivative 8b exhibited superior antioxidant activity compared to the reference standard butylated hydroxyanisole (BHA). Antimicrobial screening revealed generally low activity; however, compounds 7b and 7f showed notable inhibitory effects with MIC values of 2.5 mg/L against Staphylococcus aureus and Pseudomonas aeruginosa, respectively, while compound 8a exhibited the same MIC value against P. aeruginosa. Overall, this study demonstrates that structural modification of quinoline–sulfonamide–amino acid conjugates can influence their biological activity, highlighting compound 8b as a promising antioxidant candidate for further investigation. The docking protocol was validated by successfully re‐docking native ligands with low RMSD values (0.931–1.020 Å).