Azole-based fungicides are among the market's most widely used and effective agents. However, their indiscriminate use can lead to reduced efficacy and increased pathogen resistance. This highlights the need for novel fungicides that offer improved efficiency and lower environmental impact for controlling phytopathogenic fungi. In this study, a series of 20 novel thymol derivatives, incorporating a 1,2,3-triazole moiety, were synthesized via a three-step process, with the key step being the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The antifungal activity of these compounds was evaluated against Fusarium solani, the etiological agent of papaya fruit and stem rot. Additionally, molecular docking was performed to assess the binding energy and interaction modes of these derivatives with the F. solani lanosterol 14α-demethylase (FsCYP51) enzyme. Docking results demonstrated that all derivatives bound to the catalytic pocket of FsCYP51 with lower binding energy (<-10 kcal/mol) compared to the azole fungicide tebuconazole (-8.2 kcal/mol) and the substrate lanosterol (-9.0 kcal/mol). The observed fungicidal activity is likely due to the occupancy of the entrance tunnel and active site of the FsCYP51 by these derivatives, thereby blocking lanosterol and its conversion into ergosterol.

Keywords: 1,2,3-triazole; Fusarium solani; fungicide activity; molecular docking; papaya; thymol.

基于唑类的杀菌剂是市场上使用最广泛和效果最好的一类杀真菌剂。然而，它们的滥用可能导致效力降低以及病原体抗性的增加。这凸显了开发新型高效且对环境影响较低的杀菌剂以控制植物病原真菌的需求。在这项研究中，通过三步过程合成了20种新型百里酚衍生物，这些衍生物包含1,2,3-三氮唑基团，其中关键步骤是铜(I)催化的叠氮化物-炔烃环加成（CuAAC）反应。评估了这些化合物对导致木瓜果实和茎腐烂的病原体Fusarium solani 的抗真菌活性。此外，通过分子对接研究评估了这些衍生物与F. solani羊毛甾醇14α-去甲基酶（FsCYP51）酶的结合能和相互作用模式。对接结果表明，所有衍生物都以较低的结合能（FsCYP51 的催化口袋结合，该数值低于唑类杀菌剂丙环唑（-8.2 kcal/mol）以及底物羊毛甾醇（-9.0 kcal/mol）。观察到的杀真菌活性很可能是由于这些衍生物占据了FsCYP51 的入口隧道和活性位点，从而阻止了羊毛甾醇向麦角固醇的转化。

关键词： 1,2,3-三氮唑；Fusarium solani；杀真菌剂活性；分子对接；木瓜；百里酚。