Investigation of Nematicidal Activity, Structure–Activity Relationship, and Mechanism of C-13-Substituted Berberine Derivatives

Forty-five C-13-substituted berberine derivatives were evaluated for nematicidal activity and their structure–activity relationship (SAR). Among them, L-8 (nonyl) exhibited the most balanced broad-spectrum activity, with 48 h LC50 values of 8.58 and 6.71 μg/mL against second-stage juveniles (J2s) of Bursaphelenchus xylophilus (B. xylophilus) and Meloidogyne incognita (M. incognita), and good in vivo efficacy against M. incognita. L-8 suppressed egg hatching, feeding, and motility, and caused oxidative stress and intestinal damage. It increased MDA, decreased GSH, and inhibited defense enzymes. Mechanistic studies suggested that L-8 may affect the nematode detoxification system, including inhibition of P450 activity and potential interaction with GST. Moreover, no obvious phytotoxicity was observed. This study provides promising lead compounds for the development of novel nematicides.