Synthesis and Antibacterial, Antioxidant, and Molecular Docking Analysis of Some Novel Quinoline Derivatives

2-Chloroquinoline-3-carbaldehyde and 2-chloro-8-methylquinoline-3-carbaldehyde derivatives were synthesized through Vilsmeier formulation of acetanilide and N-(o-tolyl)acetamide. Aromatic nucleophilic substitution reaction was used to introduce various nucleophiles in place of chlorine under different reaction conditions. The carbaldehyde group was oxidized by permanganate method and reduced with metallic sodium in methanol and ethanol. The synthesized compounds were characterized by UV-Vis, IR, and NMR. The antibacterial activity of the synthesized compounds was screened against two Gram-positive bacteria (Bacillus subtilisATCC6633 andStaphylococcus aureusATCC25923) and two Gram-negative bacteria (Escherichia coliATCC 25922 andPseudomonas aeruginosaATCC 27853). Most of the compounds displayed potent activity against two or more bacterial strains. Among them, compounds6and15showed maximum activity againstPseudomonas aeruginosawith mean inhibition zones of 9.67 ± 1.11 and 10.00 ± 0.44 mm, respectively, while ciprofloxacin showed mean inhibition zone of 8.33 ± 0.44 mm at similar concentration. On the other hand, compound8exhibited maximum activity againstEscherichia coliwith inhibition zones of about 9.00 ± 0.55 mm at 300 μg/mL and 11.33 ± 1.11 mm at 500 μg/mL. The radical scavenging activity of these compounds was evaluated using 1,1-diphenyl-2-picryl hydrazyl (DPPH), and all of them displayed moderate antioxidant activity, with compound7exhibiting the strongest activity. The molecular docking study of the synthesized compounds was conducted to investigate their binding pattern with DNA gyrase, all of them were found to have minimum binding energy ranging from –6.0 to –7.33 kcal/mol, and the best result was achieved with compound11. The findings of the in vitro antibacterial and molecular docking analysis demonstrated that the synthesized compounds have potential of antibacterial activity and can be further optimized to serve as lead compounds.