Abstract
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 subtilis ATCC6633 and Staphylococcus aureus ATCC25923) and two Gram-negative bacteria (Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853). Most of the compounds displayed potent activity against two or more bacterial strains. Among them, compounds 6 and 15 showed maximum activity against Pseudomonas aeruginosa with 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, compound 8 exhibited maximum activity against Escherichia coli with 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 compound 7 exhibiting 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 compound 11. 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.
Highlights
IntroductionAntibacterial therapy has been challenging because of the alarming rate in rise of infections caused by bacteria coupled with their resistance to most of first-line antibiotic agents [1]
Antibacterial therapy has been challenging because of the alarming rate in rise of infections caused by bacteria coupled with their resistance to most of first-line antibiotic agents [1].is is a serious threat to human health of the world in the 21st century and urgently calls continuing research to find out compounds possessing better antimicrobial with broadspectrum activities
Pipemidic acid, and nalidixic acid belong to the first generation and were used for the treatment of urinary tract infection caused by the majority of Gram-negative bacteria; all of them have short lifetime [6]
Summary
Antibacterial therapy has been challenging because of the alarming rate in rise of infections caused by bacteria coupled with their resistance to most of first-line antibiotic agents [1]. Besides fluoroquinolone-based drugs, 2-chloroquinoline-3-carbaldehyde derivatives have attracted much attention due to their considerable biological and pharmacological activities including antimicrobial [8], anti-inflammatory [11,12,13], antimalarial [14, 15], anticancer [16], antiviral [17, 18], and antifungal activities [19, 20]. Inspired by these reports, we have designed and synthesized various quinoline-3-carbaldehyde derivatives and evaluated their antibacterial and radical scavenging activities. Incorporated is the in silico molecular docking analysis of the synthesized derivatives of quinolines
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