Discovery of evodiamine derivatives as potent insecticide candidates.

Evodiamine derivative 3z exhibited excellent larvicidal activities against M. separata , P. xylostella and H. armigera, and could act on the ryanodine receptor of M. separata. [Display omitted] • A series of evodiamine derivatives were rationally designed and synthesized. • 3z exhibited excellent larvicidal activities, and could be a promising potent insecticide candidate. • F atom at the E ring of evodiamine had an important effect on the larvicidal activity. • The ryanodine receptor of Mythimna separata is the potential target of 3z. In the search for novel more effective insecticides, natural products could be used as ideal template compounds due to their good environmental compatibility, various bioactivities, unique scaffolds and mode of action. We have found that natural product evodiamine, the main active component from the fruits of Evodia rutaecarpa (Juss.) Benth , displayed obvious insecticidal activities against lepidoptera pests. To continue our research, a series of evodiamine derivatives 3a-3aa were rationally designed and synthesized. The larvicidal activities results indicated that most of target compounds displayed better efficacy than evodiamine, matrine, and rotenone against Mythimna separata, Plutella xylostella and Helicoverpa armigera, among which 3z exhibited excellent larvicidal activities (65% at 2.5 mg/L against M. separata, 75% at 1.0 mg/L against P. xylostella , and 85% 10 mg/L against H. armigera , respectively), much better than evodiamine (0%), matrine (0%), and rotenone (0%). The preliminary structure activity relationships demonstrated that the fluorine atom at the E ring of evodiamine had a positive influence on the larvicidal activity. The calcium imaging experiment studies indicated that 3z could act on the ryanodine receptor (RyR) of M. separata and was an effective calcium activator for RyR. [ABSTRACT FROM AUTHOR]