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

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

doi:10.3389/fchem.2020.559262

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

Front Chem. 2020 Dec 11:8:559262. doi: 10.3389/fchem.2020.559262. eCollection 2020.

Authors

Yassine Kaddouri¹, Farid Abrigach¹, Sabir Ouahhoud², Redouane Benabbes², Mohamed El Kodadi^{1

3}, Ali Alsalme⁴, Nabil Al-Zaqri^{4

5}, Ismail Warad⁶, Rachid Touzani¹

Affiliations

¹ Laboratory of Applied Chemistry and Environment (LCAE), Faculty of Sciences, University Mohammed Premier, Oujda, Morocco.
² Laboratory of Biochemistry (LB), Department of Biology, Faculty of Sciences, University Mohamed Premier, Oujda, Morocco.
³ Centre Régional des Métiers de l'Education et de Formation Oujda, Oriental, Morocco.
⁴ Department of Chemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.
⁵ Department of Chemistry, College of Science, Ibb University, Ibb, Yemen.
⁶ Department of Chemistry, Science College, An-Najah National University, Nablus, Palestine.

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.

Keywords: DFT; Fusarium oxysporum; antifungal; docking; pyrazole; triazole.