Bioactivity-Guided Synthesis Accelerates the Discovery of Evodiamine Derivatives as Potent Insecticide Candidates

Pests threaten worldwide food security by decreasing crop yields and damaging their quality. Natural product-based molecular design and structural optimization have been one of the most effective ways to innovate pesticides for integrated insect management. To continue our previous studies on the discovery of insecticidal lead, a series of evodiamine derivatives were designed, synthesized, and evaluated for their insecticidal activities. The bioassay results demonstrated that compounds Ianand Iaoexhibited 90 and 80% insecticidal activities against Mythimna separataat 2.5 mg/L, respectively, which were superior to evodiamine (10% at 10 mg/L), matrine (45% at 600 mg/L), and rotenone (30% at 200 mg/L). Compounds Ian–Iapshowed 90% insecticidal activities against Plutella xylostellaat 1.0 mg/L, far more potent than those of evodiamine, matrine, and rotenone. Compound Iandisplayed 60% insecticidal activity against Helicoverpa armigeraat 5.0 mg/L, while evodiamine, matrine, and rotenone showed very poor activities. The study on the insecticidal mechanism of action by a calcium imaging experiment indicated that the insect ryanodine receptors (RyRs) could be the potential target of Ian. Furthermore, the molecular docking indicated that Iananchored in the binding site of the RyR of P. xylostella. The above results manifested the potential of evodiamine derivatives as potent insecticide candidates.