Research progress on structural modification and action targets of plant‐derived insecticidal active alkaloids

Abstract The severe ‘3R’ problems (Residue, Resistance, Resurgence) associated with synthetic insecticides necessitate eco‐friendly alternatives. Plant‐derived alkaloids, offering ecological compatibility, diverse modes‐of‐action and structural versatility, present promising candidates. This review synthesizes recent advances in the structural modification and insecticidal mechanisms of key plant‐derived alkaloids. For neurotoxic alkaloids, we focus on nicotine (nAChRs agonist; modifications such as bridged‐rings, e.g. cycloxaprid, reduce nontarget toxicity), matrine (Glu‐GABA signaling inhibitor; lactam ring and C‐13/14/15 modifications enhance efficacy) and evodiamine (RyRs activator; ring A/B/D/E substitutions, e.g. F, boost activity). Regarding chronic physiological inhibitors, we cover: piperine (trehalase/chitinase inhibitor disrupting molting; binding pocket optimization) and camptothecin (apoptosis inducer via mitochondrial/DNA damage; lactone ring and C‐7/10 modifications enhance cytotoxicity). The review also summarizes quinine modification strategies and sanguinarine's insecticidal mechanism. Rational structural design, guided by target structures (nAChRs, chitinases) and employing tactics such as bridged‐rings, significantly improves potency [high activity: median lethal concentration (LC 50 ) < 50 μg mL −1 ], selectivity and stability. While acknowledging synergistic effects in crude extracts, the review emphasizes that standardization and practical application require focus on optimized single bioactive constituents. Targeted structural modification is thus crucial for developing potent, selective and stable next‐generation plant‐derived alkaloid insecticides. © 2025 Society of Chemical Industry.