Synthesis, In Silico Study, and In Vitro Antifungal Activity of New 5-(1,3-Diphenyl-1-Pyrazol-4-yl)-4-Tosyl-4,5-Dihydrooxazoles.

The increase in multi-drug resistant strains has caused a sharp rise in life-threatening fungal infections in immunosuppressed patients, including those with SARS-CoV-2. Novel antifungal drugs are needed to combat multi-drug-resistant yeasts. This study aimed to synthesize a new series of 2-oxazolines and evaluate the ligands in vitro for the inhibition of six species and in silico for affinity to the CYP51 enzymes (obtained with molecular modeling and protein homology) of the same species. The 5-(1,3-diphenyl-1-pyrazol-4-yl)-4-tosyl-4,5-dihydrooxazoles were synthesized using the Van Leusen reaction between 1,3-diphenyl-4-formylpyrazoles and TosMIC in the presence of KCO or KOH without heating, resulting in short reaction times, high compound purity, and high yields. The docking studies revealed good affinity for the active site of the CYP51 enzymes of the species in the following order: > > fluconazole (the reference drug). The in vitro testing of the compounds against the species showed lower MIC values for than , and for than fluconazole, thus correlating well with the in silico findings. According to growth rescue assays, and (like fluconazole) inhibit ergosterol synthesis. The in silico toxicity assessment evidenced the safety of compounds , which merit further research as possible antifungal drugs.