AUTHOR=Wang Xiu , Duan Wengui , Lin Guishan , Li Baoyu , Chen Ming , Lei Fuhou 

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

JOURNAL=Frontiers in Chemistry

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2021.757584

DOI=10.3389/fchem.2021.757584

ISSN=2296-2646

ABSTRACT=<p>Cytochrome <italic>bc</italic><sub>1</sub> 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 <italic>bc</italic><sub>1</sub> complex as the target enzyme, twenty-three novel nopol-based 1,2,4-triazole-thioether compounds were designed and synthesized from natural preponderant resource <italic>β</italic>-pinene, and their structures were confirmed by FT-IR, NMR, ESI-MS and elemental analysis. The <italic>in vitro</italic> antifungal activity of the target compounds <bold>5a-5w</bold> 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 <italic>Physalospora piricola</italic>, in which compounds <bold>5b</bold> (R= <italic>o</italic>-CH<sub>3</sub> Ph), <bold>5e</bold> (R= o-OCH<sub>3</sub> Ph), <bold>5h</bold> (R= <italic>o</italic>-F Ph), <bold>5m</bold> (R= <italic>o</italic>-Br Ph), <bold>5o</bold> (R= <italic>m,m</italic>-OCH<sub>3</sub> Ph), and <bold>5r</bold> (R= <italic>p</italic>-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 <bold>5a</bold> (R= Ph) had inhibition rate of 87.9% against <italic>Rhizoeotnia solani</italic>, and compound <bold>5b</bold> (R= <italic>o</italic>-CH<sub>3</sub> Ph) had inhibition rates of 87.6 and 89% against <italic>Bipolaris maydis</italic> and <italic>Colleterichum orbicala</italic>, respectively. In order to develop novel and promising antifungal compounds against <italic>P. piricola</italic>, 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 (<italic>r</italic><sup><italic>2</italic></sup> = 0.944, <italic>q</italic><sup><italic>2</italic></sup> = 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 <italic>bc</italic><sub>1</sub> complex.</p>