Synthesis, structural characterization, computational studies, and antifungal activity of isoniazid derivative

Abstract

In this work, the isoniazid derivative N',N'''-((1E,1′E)-1,4-phenylenebis(methaneylylidene))di(isonicotinohydrazide) (BISHDZHI) was synthesized and characterized by Nuclear Magnetic Resonance (NMR), Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR), Fourier Transform Raman (FT-Raman), and Ultraviolet-Visible (UV–Vis) spectroscopy, and its potential against fungal strains of Candida ssp. was evaluated by in vitro assays. The NMR spectrum confirmed the molecular structure of BISHDZHI. Quantum chemistry computational calculations allowed to obtain the potential energy surface, optimized molecular structure, and to identify all the bands of the Raman, infrared and UV spectra. The data calculated for isoniazid derivative BISHDZHI using the Functional Density Theory (DFT) are in accordance with the experimental values. Our in vitro studies showed that the BISHDZHI compound in association with Fluconazole possesses antifungal action against Candida tropicalis strain, with a reduction of the IC50 24 times to the host. In silico study of ADMET suggested that BISHDZHI has excellent oral bioavailability and metabolic stability, which allows therapeutic action without severe risk to the host. In addition, the molecular docking showed a high interaction potential between the Candida Albicans target. While the molecular dynamics simulations suggested that the BISHDZHI ligand occasioned a minor change in the structure target, indicating more excellent stability than the drug fluconazole.