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)

Molecules

Rodrigo Abonia¹  Cristian Rocha-Roa²  Jovanny A. Gómez Castaño³  Andrés Restrepo-Acevedo⁴  Ronan Le Lagadec⁴  Dorancelly Fernandez⁵  Fernando Cuenú-Cabezas⁵  Susana A. Zacchino⁶ 

[1] Departamento de Química, Universidad del Valle, Calle 13 No. 100-00, A.A. 25360, Cali 76001, Colombia;Grupo GEPAMOL, Centro de Investigaciones Biomédicas, Universidad del Quindío, Carrera 15, Calle 12 Norte, Armenia 630004, Colombia;Grupo Química-Física Molecular y Modelamiento Computacional (QUIMOL®), Facultad de Ciencias, Universidad Pedagógica y Tecnológica de Colombia (UPTC), Avenida Central del Norte, Tunja, Boyacá 050030, Colombia;Instituto de Química UNAM, Circuito Exterior s/n, Ciudad Universitaria, Ciudad de México 04510, Mexico;Laboratorio de Química Inorgánica y Catálisis, Programa de Química, Universidad del Quindío, Carrera 15, Calle 12 Norte, Armenia 630004, Colombia;Área Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario (UNR), Suipacha 531, Rosario S2002LRK, Argentina;

关键词: Schiff bases;    azomethine compounds;    Candida albicans;    Cryptococcus neoformans;    in silico studies;    molecular docking;   

DOI  :  10.3390/molecules26247435

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown