Data_Sheet_1_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.PDF

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.

本研究合成了12种新近报道的化合物，其分子结构中包含吡唑（pyrazole）、噻唑（thiazole）、三唑（triazole）及苯并三唑（benzotriazole）等多种杂环官能团，产物收率优异，最高可达37%~99.6%。随后针对尖孢镰刀菌萎蔫专化型（Fusarium oxysporum f. sp. albedinis，即巴尤德病致病菌）开展抑菌活性测试，其中化合物2、4、5表现最优，其半最大抑制浓度（IC50）为18.8~54.4 μg/mL。本研究通过密度泛函理论（DFT）分析了各化合物的分子反应活性；同时针对包含全部57个受试化合物的数据集，开展分子对接模拟，以阐明受试化合物与作为生物靶点的尖孢镰刀菌植酸酶结构域（Fophy）之间的相互作用协同机制。通过对比Fophy蛋白的分子对接结果可知，化合物5的结合亲和力最优，其次为化合物2与4，该结果与实验测得的IC50值趋势高度吻合：IC50大小顺序为74.28（化合物5）<150（化合物2）<214.10（化合物4）。本研究通过对同源建模蛋白进行盲对接/虚拟筛选，结合Autodock Vina与Dockthor网页工具两款不同软件，得到了潜在结合位点，可为后续抗真菌药物的开发提供参考依据。