DESIGN, SYNTHESIS AND MOLECULAR DOCKING STUDY OF HYBRID QUINOLINE-4-YL-OXADIAZOLES/OXATHIADIAZOLES AS POTENT ANTIFUNGAL AGENTS
Keywords:
Quinoline, Oxadiazole, Oxathiadiazole, Antifungal activity, Molecular docking study, NilAbstract
Objective: The aim of the present work was to design and synthesize hybrid quinoline-4-yl-oxadiazoles/oxathiadiazole derivatives and evaluate them for in vitro antifungal activity against human disease causing pathogens.
Methods: The compounds 5(a-d), 6(a-d) and 7(a-d) were efficiently synthesized in good yields. The synthesized compounds were characterized using 1H NMR, 13C NMR and Mass spectra. The synthesized compounds were screened for in vitro antifungal activity and minimum inhibitory concentration (MIC) values were determined using standard agar method. Molecular docking study was performed against fungal enzyme P450 cytochrome lanosterol 14α-demethylase using VLife MDS 4.3 software.
Results: The synthesized compounds had shown good to moderate in vitro antifungal activity. The compound 6a (MIC range = 15-25 µg/ml) from 1,2,3,5-oxathiadiazole-2-oxide series showed most potent activity amongst the synthesized compounds when compared with standard clotrimazole (MIC range = 12.5-25 µg/ml). The molecular docking study of synthesized compounds showed good binding interactions against active site of fungal enzyme P450 cytochrome lanosterol 14α-demethylase.
Conclusion: The results of in vitro antifungal activity and molecular docking study revealed that the synthesized compounds have potential antifungal activity and can be further optimized and developed as a lead compound.
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