Design, Synthesis, and Action Mechanism of 3-Carene-Based Acylhydrazone Compounds as Potential Novel Herbicidal Candidates

In an attempt to discover natural-product-derived novel green herbicides, 26 novel 3-carene-based acylhydrazone compounds were designed and synthesized. Their chemical structures were characterized by FTIR, NMR, HRMS, NOESY, and single-crystal X-ray diffraction. The herbicidal activity of the target compounds was evaluated, and the target compound AH18 exhibited good herbicidal activity against the dicotyledonous plant Brassica campestris and the monocotyledonous plant Echinochloa crusgalli L. The EC 50 values of its herbicidal activity against the two tested plants were better than or similar to those of the positive control diuron. The structure–activity relationship of compounds AH18 and AH24 was investigated by DFT theoretical calculation. The action mechanism of herbicidal activity was explored through various methods including the inhibitory activity of laccase, fluorescence quenching of laccase, chelating property of compound AH18 to Cu 2+, molecular docking, and molecular dynamic simulation. Furthermore, the cytotoxicity of compound AH18 against normal human kidney cells (HEK293T cells) was also preliminarily evaluated. All of these results showed that compound AH18 may exert its good herbicidal activity by inhibiting laccase. Therefore, it deserves further investigation as a promising novel low-toxicity green herbicidal lead compound.