Synthesis and Pharmacological Screening of Difluorophenyl Pyrazole Chalcone Conjugates as Antifungal, Anti-Inflammatory, and Antioxidant Agents

A new series of difluoro phenyl pyrazole chalcone was prepared by utilizing PEG 400 as a catalyst and investigated for their antifungal, anti-inflammatory, and antioxidant activity. The compounds 3-[3-(4-bromo-phenyl)-1-phenyl-1H-pyrazol-4-yl]-1-(2,4-difluloro-phenyl)-propenone (IVc), 1-(2,4-difluoro-phenyl)-3-[3-(4-methyl-phenyl)-1-phenyl-1H-pyrazol-4-yl]-propenone (IVd), 1-(2,4-difluoro-phenyl)-3-[3-(4-methoxy-phenyl)-1-phenyl-1H-pyrazol-4-yl]-propenone (IVe), and 1-(2,4-difluoro-phenyl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)-propenone (IVg) exhibited promising antifungal activity at MIC of 25 and 50 μg/mL against selected human pathogenic fungi. Synthesized compounds 1-(2,4-difluoro-phenyl)-3-[3-(4-methoxy-phenyl)-1-phenyl-1H-pyrazol-4-yl]-propenone (IVe), 1-(2,4-difluoro-phenyl)-3-[3-(4-methyl-phenyl)-1-phenyl-1H-pyrazol-4-yl]-propenone (IVd), 1-(2,4-difluoro-phenyl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)-propenone (IVg) and 1-(2,4-difluoro-phenyl)-3-[3-(4-fluoro-phenyl)-1-phenyl-1H-pyrazol-4-yl]-propenone (IVa) showed good anti-inflammatory activities comparable to the standard drug diclofenac sodium. Compounds 1-(2,4-difluoro-phenyl)-3-[3-(4-methoxy-phenyl)-1-phenyl-1H-pyrazol-4-yl]-propenone (IVe), 1-(2,4-difluoro-phenyl)-3-[3-(4-methyl-phenyl)-1-phenyl-1H-pyrazol-4-yl]-propenone (IVd) and 1-(2,4-difluoro-phenyl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)-propenone (IVg) showed good hydrogen peroxide scavenging potential as compared to the butylated hydroxyl toluene. The conjugates 1-(2,4-difluoro-phenyl)-3-[3-(4-methoxy-phenyl)-1-phenyl-1H-pyrazol-4-yl]-propenone (IVe), 1-(2,4-difluoro-phenyl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)-propenone (IVg), and 1-(2,4-difluoro-phenyl)-3-[3-(4-methyl-phenyl)-1-phenyl-1H-pyrazol-4-yl]-propenone (IVd) found more potent than standard ascorbic acid in DPPH radical scavenging assay as well as ferrous reducing power assay. The conjugates showed good interactions with the target protein in docking study.