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)

Abstract

The azo-azomethine imines, R1-N=N-R2-CH=N-R3, are a class of active pharmacological ligands that have been prominent antifungal, antibacterial, and antitumor agents. In this study, four new azo-azomethines, R1 = Ph, R2 = phenol, and R3 = 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.

Silver and Antimicrobial Polymer Nanocomplexes to Enhance Biocidal Effects

“…The sterol 14-alpha demethylase enzyme plays a major role in the biosynthesis of ergosterol, which is important for the growth of fungi and essential for the synthesis of fungal cell membranes. Therefore, it is considered a molecular target for antifungal experiments, especially for C. albicans [88,89]. Even though azoles (important antifungal drugs) also target the 14-alpha demethylase enzyme, in this situation, DA can assist in interacting with the fungal cell wall.…”

Mechanochemical Synthesis of Fluorinated Imines

“…Due to its ability to undergo interactions with a wide range of biological targets, the imine function is an essential pharmacophore in nitrogen-containing bioactive compounds [6][7][8][9][10]. There are many different pharmacophores.…”