RESUMO
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.
Assuntos
Antifúngicos , Candida albicans/crescimento & desenvolvimento , Cryptococcus neoformans/crescimento & desenvolvimento , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Pirazóis , Antifúngicos/síntese química , Antifúngicos/química , Antifúngicos/farmacologia , Pirazóis/síntese química , Pirazóis/química , Pirazóis/farmacologiaRESUMO
In the title compound, C(13)H(16)N(4)O(2), the pyrazole ring forms a dihedral angle of 50.61â (6)° with the 3-nitro-phenyl ring. The plane of the nitro group is twisted by 6.8â (7)° out of the plane of the phenyl ring. In the crystal, the mol-ecules are linked by N-Hâ¯N and N-Hâ¯O hydrogen bonds, forming sheets in the bc plane. In addition, a weak C-Hâ¯N inter-action is observed.