AUTHOR=Kaddouri Yassine , Abrigach Farid , Ouahhoud Sabir , Benabbes Redouane , El Kodadi Mohamed , Alsalme Ali , Al-Zaqri Nabil , Warad Ismail , Touzani Rachid 

TITLE=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

JOURNAL=Frontiers in Chemistry

VOLUME=8

YEAR=2020

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2020.559262

DOI=10.3389/fchem.2020.559262

ISSN=2296-2646

ABSTRACT=<p>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 <italic>Fusarium oxysporum f</italic>. sp. <italic>albedinis</italic> fungi (Bayoud disease), where the best results are for compounds <underline><bold>2</bold></underline>, <underline><bold>4</bold></underline>, and <underline><bold>5</bold></underline> with IC<sub>50</sub> = 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 <italic>F. oxysporum</italic> phytase domain (Fophy) enzyme as biological target. By comparing the results of the docking studies for the Fophy protein, it is found that compound <underline><bold>5</bold></underline> has the best affinity followed by compounds <underline><bold>2</bold></underline> and <underline><bold>4</bold></underline>, so there is good agreement with the experimental results where their IC<sub>50</sub> values are in the following order: 74.28 (<underline><bold>5</bold></underline>) &lt; 150 (<underline><bold>2</bold></underline>) &lt; 214.10 (<underline><bold>4</bold></underline>), 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.</p>