Mono-Alkylated Ligands Based on Pyrazole and Triazole Derivatives Tested Against Fusarium oxysporum f. sp. albedinis: Synthesis, Characterization, DFT, and Phytase Binding Site Identification Using Blind Docking/Virtual Screening for Potent Fophy Inhibitors

Abstract

Twelve recent compounds, incorporating several heterocyclic moieties such as pyrazole, thiazole, triazole, and benzotriazole, made in excellent yield up to 37–99.6%. They were tested against Fusarium oxysporum f. sp. albedinis fungi (Bayoud disease), where the best results are for compounds 2, 4, and 5 with IC50 = 18.8–54.4 μg/mL. Density functional theory (DFT) study presented their molecular reactivity, while the docking simulations to describe the synergies between the trained compounds of dataset containing all the tested compounds (57 molecules) and F. oxysporum phytase domain (Fophy) enzyme as biological target. By comparing the results of the docking studies for the Fophy protein, it is found that compound 5 has the best affinity followed by compounds 2 and 4, so there is good agreement with the experimental results where their IC50 values are in the following order: 74.28 (5) < 150 (2) < 214.10 (4), using Blind docking/virtual screening of the homology modeled protein and two different tools as Autodock Vina and Dockthor web tool that gave us predicted sites for further antifungal drug design.

Synthesis, Crystal Structures, Genotoxicity, and Antifungal and Antibacterial Studies of Ni(II) and Cd(II) Pyrazole Amide Coordination Complexes

“…In particular, C 2 exhibits a remarkable inhibition of 96% even at low concentrations (78.9 µmol/L) compared to all other compounds, including cycloheximide. Its characteristics overcome reported values for ligand molecules [ 46 , 47 ] in addition to other Cd and Ni coordination complexes ( Table 3 ). The anti-Fusarium inhibition activity of our C 2 is also comparable to the remarkable inhibition properties of two dinuclear Co and Cu complexes reported recently [ 38 , 44 ].…”

“…To assess the genotoxicity of L 1 and L 2 as well as of the coordination complexes C 1 and C 2 , we report the tail intensity, tail length, and tail moment (see Figure 3 ). For the sake of comparison, we compare their genotoxicity with hydrogen peroxide, which is known for being a typical DNA-damage-inducing agent [ 47 ]. L 1 and L 2 have weak genotoxicity compared to the negative control, whereas an increase in genotoxicity is found for C 1 and C 2 in comparison to hydrogen peroxide.…”

New N-Alkylated Heterocyclic Compounds as Prospective NDM1 Inhibitors: Investigation of In Vitro and In Silico Properties

“…Blind docking/virtual screening was considered to target the previous protein (5ZGE), which was prepared in Autodock 4 [ 115 ] default parameters, and the whole protein was used for the grid box ( Table S1 ), with Perl as a launcher for all the ligands in Autodock Vina [ 116 , 117 , 118 , 119 , 120 ].…”

Critical Evaluation of Biocontrol Ability of Bayoud Infected Date Palm Phyllospheric Bacillus spp. Suggests That In Vitro Selection Does Not Guarantee Success in Planta

“…To date, no curative treatment exists against this fungus [19]. The means recommended against the disease are chemical control (use of fungicides, eradication, and incineration of the palm, soil disinfestation by solarization, and fumigation).…”