Synthesis, Structural Characterization, and In Vitro and In Silico Antifungal Evaluation of Azo-Azomethine Pyrazoles (PhN2(PhOH)CHN(C3N2(CH3)3)PhR, R = H or NO2)

The azo-azomethine imines, R-1-N=N-R-2-CH=N-R-3, are a class of active pharmacological ligands that have been prominent antifungal, antibacterial, and antitumor agents. In this study, four new azo-azomethines, R-1 = Ph, R-2 = phenol, and R-3 = pyrazol-Ph-R' (R = H or NO2), have been synthesized, structurally characterized using X-ray, IR, NMR and UV-Vis techniques, and their antifungal activity evaluated against certified strains of Candida albicans and Cryptococcus neoformans. The antifungal tests revealed a high to moderate inhibitory activity towards both strains, which is regulated as a function of both the presence and the location of the nitro group in the aromatic ring of the series. These biological assays were further complemented with molecular docking studies against three different molecular targets from each fungus strain. Molecular dynamics simulations and binding free energy calculations were performed on the two best molecular docking results for each fungus strain. Better affinity for active sites for nitro compounds at the meta and para positions was found, making them promising building blocks for the development of new Schiff bases with high antifungal activity.

Automated summary

In this study, four new azo-azomethines were synthesized and characterized, showing high to moderate inhibitory activity against Candida albicans and Cryptococcus neoformans. Molecular docking studies indicated that nitro compounds at meta and para positions have better affinity for active sites, making them promising candidates for developing highly active antifungal Schiff bases.