Synthesis of some quinoline-pyrazoline-based naphthalenyl thiazole derivatives and their evaluation as potential antimicrobial agents

Abstract

Purpose: To prepare and evaluate some quinoline-pyrazoline-based naphthalenyl thiazole derivatives as antimicrobial agents. Methods: Some quinoline-pyrazoline-based naphthalenyl thiazoles ( 5a-5e and 6a-6e ) were prepared by reacting 5-(2-chloroquinolin-3-yl)-3-substitutedphenyl-4,5-dihydro-1H-pyrazole-1-carbothiamides (4a- 4e) with 2-bromo-1-(1-naphthyl)ethanone and 2-bromo-1-(2-naphthyl)ethanone, respectively. Fourier transform infra-red (FTIR), 13 C-Nuclear magnetic resonance ( 13 C-NMR), 1 H-Nuclear magnetic resonance ( 1 H-NMR), elemental analysis, and mass spectrometry were used to elucidate and confirm the chemical structures of the target compounds. Serial plate dilution technique was used to evaluate the antimicrobial activity of the title compounds using ketoconazole and ofloxacin as standards, and their minimum inhibitory concentrations (MIC) were determined. Results: A total of ten compounds, ( 5a-5e ) & ( 6a-6e ) were prepared. Compound 6d (R = 4-F, naphthalen-2-yl derivative) exhibited antimicrobial activities that were higher than those of the standard drug (ofloxacin) against S. aureus (MIC = 25 μg/mL, p < 0.05), S. epidermidis (MIC = 25 μg/mL, p < 0.0001), K. pneumonia (MIC = 25 μg/mL, p < 0.0001), P. vulgaris (MIC = 25 μg/mL, p < 0.0001) and P. citrinum (MIC = 25 μg/mL, p < 0.0001). Compound 5d (R = 4-F, naphthalen-1-yl derivative) displayed higher antifungal activity than ketoconazole against C. albicans (MIC = 25 μg/mL, p <0.0001). Conclusion: The naphthalen-2-yl derivatives (6a-6e) are superior antimicrobial agents as compared to the naphthalen-1-yl derivatives (5a-5e) and the presence of 4-F substituent in 6d and 5d is essential for stronger antimicrobial activity. The compound 6d needs further investigations related to its safety and efficacy. Keywords: Quinoline, Pyrazoline, Thiazole, Antibacterial, Antifungal, Structure-activity relationship