Synthesis, 3D-QSAR and Molecular Docking Study of Nopol-Based 1,2,4-Triazole-Thioether Compounds as Potential Antifungal Agents

• Published in: Frontiers in chemistry 2021-10, Vol.9, p.757584-757584
• Main Authors: Wang, Xiu, Duan, Wengui, Lin, Guishan, Li, Baoyu, Chen, Ming, Lei, Fuhou
• Format: Article
• Language: English
• Subjects: 1, 2, 4-triazole-thioether; 3D-QSAR; Chemistry; molecular docking; nopol; β-pinene
• ISSN: 2296-2646; 2296-2646
• DOI: 10.3389/fchem.2021.757584

Cytochrome complex is an important component of cellular respiratory chain, and it is also an important target enzyme to inhibit the growth of plant pathogens. Using cytochrome complex as the target enzyme, twenty-three novel nopol-based 1,2,4-triazole-thioether compounds were designed and synthesized from natural preponderant resource -pinene, and their structures were confirmed by FT-IR, NMR, ESI-MS and elemental analysis. The antifungal activity of the target compounds was preliminarily evaluated against eight plant pathogens at the concentration of 50 µg/ml. The bioassay results showed that the target compounds exhibited the best antifungal activity against , in which compounds (R= -CH Ph), (R= o-OCH Ph), (R= -F Ph), (R= -Br Ph), (R= -OCH Ph), and (R= -OH Ph) had inhibition rates of 91.4, 83.3, 86.7, 83.8, 91.4 and 87.3%, respectively, much better than that of the positive control chlorothalonil. Also, compound (R= Ph) had inhibition rate of 87.9% against , and compound (R= -CH Ph) had inhibition rates of 87.6 and 89% against and , respectively. In order to develop novel and promising antifungal compounds against , the analysis of three-dimensional quantitative structure-activity relationship (3D-QSAR) was carried out using the CoMFA method on the basis of their antifungal activity data, and a reasonable and effective 3D-QSAR model ( = 0.944, = 0.685) has been established. In addition, the theoretical study of molecular docking revealed that the target compounds could bind to and interact with the site of cytochrome complex.