Discovery of Trifluorobutene Amide Derivatives as Potential Nematicides: Design, Synthesis, Nematicidal Activity Evaluation, SAR, and Mode of Action Study

Abstract

Plant-parasitic nematodes are one of the major threats to crop protection. However, only limited nematicides are currently available and are confronted with a growing resistance problem, which necessitates the development of novel nematicides. In this study, a series of trifluorobutene amide derivatives was synthesized through the strategy of amide bond reversal, and their nematicidal activity against Meloidogyne incognita was evaluated. The bioassay showed that compounds C2, C10, and C18 and some analogues thereof exhibited good nematicidal activity. Among them, the derivatives of compound C2 containing a benzene ring [C26 (R = 2-CH 3 ) and C33 (R = 2-Cl)] exhibited excellent bioactivity against M. incognita in vitro. The LC 50/72h values reached 14.13 and 14.71 mg•L −1 , respectively. Moreover, analogues of compounds C10 and C18 containing a thiophene ring [C43 (R = 5-CH 3 ), C44 (R = 4-CH 3 ), and C50 (R = 5-Cl)] exhibited significant bioactivity against M. incognita in vivo with inhibition rates of 68.8, 65.5, and 69.8% at 2.5 mg•L −1 in a matrix, respectively. Meanwhile, C44 and C50 also showed excellent control effects against M. incognita in both cups and microplots. The structure−activity relationship (SAR) of synthesized compounds was discussed in detail. Comparative molecular field analysis (CoMFA) was also conducted to develop the SAR profile. The preliminary mode of action investigation showed that compound C33 exhibited strong inhibition on egg hatching, motility, feeding behavior, and growth of Caenorhabditis elegans. At the same time, the impact of active compounds on biochemical indicators related to oxidative stress showed that compound C33 influenced the production of ROS (reactive oxygen species), and the accumulation of lipofuscin and lipids on C. elegans.