Synthesis, Molecular Docking Studies and Evaluation of Antibacterial and Antioxidant Activities Fluoroquinoline Derivatives

Abstract

Quinoline is a ubiquitous structural feature that occurs in several natural compounds and pharmacologically active substances displaying a broad range of biological activities such as anti bacterial, anti-malarial, anti-microbial, ant-inflammatory, anti-convulsant, anti-cancer and anti mycobacterial activity. The aim of this project was to synthesize and evaluate antibacterial and antioxidant activities of the quinoline derivatives. In this project 8 quinoline derivatives were synthesized. The characterization of the synthesized compounds were carried out by melting point and spectroscopic technique ((UV-Vis, 1H, 13C and DEPT-135 NMR). The synthesized compounds were screened for their antibacterial activities by disc diffusion method against E. coli, S. aureus, S.pyogene and P. aeruginosa. Ciprofloxacin and DMSO were used as reference drugs and negative control, respectively. Compounds 86, 87, 88 and 89 showed antibacterial activity with IZ of 14.7±0.04 mm, 13.0±0.53mm, 13.2±0.3mm, and 12.9±0.33mm against S. pyogene, respectively, whereas compounds 90, 96 and 97 showed IZ value of 10.4±0.66mm, 7.9±0.45mm, and 8.0±0.55mm against P. aeruginosa at 200 μg, respectively. Compound 91 showed IZ value of 11.1±0.07mm against E. coli at 200 μg all compared to ciprofloxacin with IZ of 18.2±0.34mm against S.pyogene, 10.0±0.45mm against P. aeruginosa and 11.1±0.07mm against E.coli at the same concentration. Molecular docking of synthesized compounds was assessed against DNA gyrase B and Human Topoisomerase IIα. The synthesized compounds were found to have binding affinity ranging from -6.8 to -7.5 (kcal/mol) with best result achieved for 87 (-7.2 kcal/mol), 88 (-7.2 kcal/mol), 91 (-7.4 kcal/mol) and 96 (-7.5 kcal/mol). Radical scavenging activity of synthesized compounds was evaluated using DPPH. Compounds 86, 87,88,89,90 and 91 have strong antioxidant activity with 62.5%, 61.43%, 71.12%, 73.32%, 57.78% and 66.09% respectively, compared to ascorbic acid 87.06%. From these compounds compound 89(73.32 %,) was strong. IC50 varies from 5.31 μg/mL for compound 89 to 16.71 μg/mL for compound 96. Compound 89 (5.31 μg/mL) showed strong antioxidant activity. Hence compound 87, 88, 91 and 96 might be used for further studies.