Synthesis, characterization and bio-evaluation of novel series of pyrazoline derivatives as potential antifungal agents

In this study, a series of novel α, β-unsaturated carbonyl compounds (3a-j) and their pyrazoline derivatives (4a-e and 5a-b) were designed and successfully synthesized. All synthesized compounds were characterized using various spectroscopic techniques, including ¹H NMR, ¹³C NMR, and mass spectrometry. The biological activity of these compounds was evaluated against five bacterial strains (Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, and Acinetobacter baumannii) and three fungal strains (Candida tropicalis, Candida parapsilosis, and Candida albicans). The results revealed that compound (4c) exhibited potent antifungal activity with a minimum inhibitory concentration (MIC) of 6.25 µg/mL across all tested strains and zone of inhibition (ZOI) against Candida albicans is 27 mm. Furthermore, time kill kinetics of Candida albicans and haemolysis assays also perform in support of their antifungal activity. Additionally, all synthesized compounds were subjected to computational analysis using molecular descriptors, ADMET, molecular docking, and molecular dynamics to find protein-ligand interactions. Molecular docking studies indicated that the most effective antifungal compounds (3h and 4c) exhibited binding energies of -8.76 and -8.44 kcal/mol for DHFR and -7.96 and -8.24 kcal/mol for NMT1, respectively. The obtained results revealed that these compounds exhibit potential interactions with antifungal targets as dual inhibitors. As a result, this study finds an important approach to synthesized compounds with potential antifungal activity.