Synthesis, biological evaluation, and molecular docking of novel ferulic acid derivatives containing a 1,3,4-oxadiazole thioether and trifluoromethyl pyrimidine skeleton

Jiansong An; Nianjuan Pan; Chunyi Liu; Haijiang Chen; Qiang Fei; Xiuhai Gan; Wenneng Wu

doi:10.1039/d4ra01765j

Synthesis, biological evaluation, and molecular docking of novel ferulic acid derivatives containing a 1,3,4-oxadiazole thioether and trifluoromethyl pyrimidine skeleton

RSC Adv. 2024 May 20;14(23):16218-16227. doi: 10.1039/d4ra01765j. eCollection 2024 May 15.

Authors

Jiansong An¹, Nianjuan Pan¹, Chunyi Liu¹, Haijiang Chen¹, Qiang Fei¹, Xiuhai Gan², Wenneng Wu¹

Affiliations

¹ School of Food Science and Engineering, Guiyang University Guiyang 550005 China wuwenneng123@126.com.
² National Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University Guiyang 550025 China.

Abstract

In this study, 24 novel ferulic acid derivatives containing 1,3,4-oxadiazole thioether and trifluoromethyl pyrimidine were designed and synthesized. Bioactivity assay showed that some of the target compounds exhibited moderate to good antifungal activity against Botryosphaeria dothidea BD), Phomopsis sp. (PS), Botrytis cinerea (BC), Fusarium spp. (FS), Fusarium graminearum (FG), and Colletotrichum sp. (CS). Especially, compound 6f demonstrated superior antifungal activity against Phomopsis sp., with an EC₅₀ value of 12.64 μg mL^-1, outperforming pyrimethanil (35.16 μg mL^-1) and hymexazol (27.01 μg mL^-1). Meanwhile, compound 6p showed strong antibacterial activity against X. axonopodis pv. citri (XAC) in vitro, with an inhibition ratio of 85.76%, which was higher than thiodiazole copper's 76.59% at 100 μg mL^-1. Furthermore, molecular docking simulations elucidated that compound 6f engaged in hydrogen bonding with the succinate dehydrogenase (SDH) enzyme at SER-17, SER-39, ARG-14 and ARG-43 sites, clarifying its mode of action. This study highlights the potential of these novel ferulic acid derivatives as promising agents for controlling fungal and bacterial threats to plant health. To the best of our knowledge, this study represents the first report on the antifungal and antibacterial properties of ferulic acid derivatives containing 1,3,4-oxadiazole thioether and trifluoromethyl pyrimidine skeleton.