Synthesis And Evaluation Of The Antibacterial And Antioxidant Activities And In Silico Molecular Docking Analysis Of Quinoline Derivatives

Abstract

The quinoline heterocycle is a useful scaffold to develop bioactive molecules. In the present work, a series of novel quinoline derivatives were synthesized by Vilsmeier–Haack reaction. Methoxy and Ethoxyl (nucleophiles) were introduced into 2,7-dichloroquinoline-3-carbaldehyde by substitution of chlorine at 2-position using potassium carbonate in DMF. The carbaldehyde functional group of 2,7-dichloroquinoline-3-carbaldehyde and 2-chloroquinoline-3- carbaldehyde was further manipulated to nitriles using phosphorous oxychloride and sodium azide. The nitrile functional group of 2,7-dichloroquinoline-3-carbonitrile was converted to amide using acetic acid and sulfuric acid. All synthesized compounds were characterized by 1 H NMR, 13C NMR, and UV-Vis spectroscopy. The antibacterial activity of the synthesized compounds (129-133) were screened against two Gram negative (E. coli and P. aeruginosa) and two Gram positive (S. aureus and S. pyogenes) pathogenic bacteria. Most of the compounds displayed good activity against two or more bacterial strains. Among them, compounds 132 and 130 showed good activities against E. coli with mean inhibition zones of 12.00 ± 0.00 and 11.00 ± 0.04 mm respectively. The compound 129 also had good activity against S. aureus and P. aeruginosa with mean inhibition of 11.00 ± 0.03 mm at 200 µg/mL relative to standard amoxicillin. Compound 131 at 200 µg/mL concentration showed good activity against S. pyrogenes with mean inhibition of 11.00 ± 0.02 mm. The radical scavenging activity of these compounds was evaluated using 1,1-diphenyl-2-picryl hydrazyl (DPPH), and compounds 130 and 129 displayed strongest antioxidant activity with IC50 of 0.31 and 2.17 µg/mL relative to ascorbic acid (2.41 µg/mL) respectively. The molecular docking study of the synthesized compounds was conducted to investigate their binding pattern with topoisomerase IIα or anticancer potency and E. coli gyraseB. The in silico interaction results match with the in vitro analysis of the synthesized compounds showed good activities against E. coli, among synthesized compounds 130 (-6.4 kcal/mol) and 132 (-6.6 kcal/mol) exhibited better activity. The synthesized compounds (129-133) were found to have minimum binding energy ranging from -6.9 to -7.3 kcal/mol against topoisomerase IIα, with best results achieved with compound 132 (-7.3 kcal/mol), 129 (-7.1 kcal/mol) and 130 (-7.1 kcal/mol) of these, compound 132 displayed binding affinity of -7.3 Kcal/mol compared to vosaroxin (-7.2 Kcal/mol).