Azole-containing compounds as inhibitors of Fusarium enzyme-based targets by docking analyses

Fusarium is a genus of fungal organisms that cause devastating diseases of several crops whose worldwide incidence is growing. Currently there is no agreeable method of combating this pathogen. However, research on antifungal agents through exploration for natural sources of bioactive substances has led to important advances. Azole-containing compounds are metabolites produced by several organisms having a wide-range of activities and they are considered as important moieties for development of fungicides, mostly due to a possible action on several enzyme-based targets such as sterol 14α-demethylase, trichodiene synthase, trichothecene 15-O-acetyltransferase, α-L-fucosidase, α-L-arabinofuranosidase, nitric oxide reductase, and ribonuclease F1. As part of our research on antifungal compounds, a set of synthetic and naturally-occurring azole-containing compounds were in silico evaluated through molecular docking using Autodock/Vina. Thus, the most stable conformers from MMFF-level optimized structures of test compounds were docked within the active sites of the above-mentioned enzyme-based targets. Binding modes between enzymes and test compounds were investigated through Vina scores and ligand-residues interactions. Good Vina scores were obtained for docked structures at different levels. In addition, the results indicated that the best poses were found to be different for each test compound as well as the residues involved into the ligand-enzyme binding. Most stable conformers of VNI and azole 1 were found to exhibit comparable docking energies to than of controls (docking energies within -8.0 – -12.0 kcal/mol range). Azole-containing compounds might be considered as good candidates for structural optimization leading natural product-based design of anti-phytopathogens. The present work is a product derived by the Project CIAS-1331 financed by Vicerrectoría de Investigaciones at UMNG – Validity 2013.