Synthesis, Biochemical Characterization, and Theoretical Studies of Novel β-Keto-enol Pyridine and Furan Derivatives as Potent Antifungal Agents

In the present study, we report the design and synthesis of new derivatives of the β-keto-enol grafted on pyridine and furan moieties (L 1 -L 11 ). Structures of compounds were fully confirmed by Fourier transform infrared spectroscopy (FT-IR), 1H NMR, 13C NMR, electrospray ionization/liquid chromatography-mass spectrometry (ESI/LC-MS), and elemental analysis. The compounds were screened for antifungal and antibacterial activities (Escherichia coli, Bacillus subtilis, and Micrococcus luteus). In vitro evaluation showed significant fungicidal activity for L 1 , L 4 , and L 5 against fungal strains (Fusarium oxysporum f.sp albedinis) compared to the reference standard. Especially, the exceptional activity has been demonstrated for L 1 with IC50 = 12.83 μg/mL. This compound and the reference benomyl molecule also showed a correlation between experimental antifungal activity and theoretical predictions by Petra/Osiris/Molinspiration (POM) calculations and molecular coupling against the Fgb1 protein. The highest inhibition of bacterial growth for L 1 is due to its strongest binding to the target protein. This report may stimulate the further synthesis of examples of this substance class for the development of new drugs.