Chemical Modifications of an Insect Immune Resolvin, EpOME, to a Broad-Spectrum Lepidopteran-Specific Insecticide

EpOMEs suppress excessive and unnecessary immune responses at late infection stage in insects. This immune resolvin activity of EpOMEs includes the cell lysis of hemocytes by causing apoptosis. This cytolytic toxicity of EpOMEs suggests a potential insecticidal activity of their stable analogs. In fact, a propoxy derivative of 12,13-EpOME called AS56 mimicked EpOME activity by suppressing immune responses and exhibited insecticidal activity against a lepidopteran insect, Spodoptera exigua. This study evaluated the potency of the EpOME analogs by modifying their functional groups. PD28 is a racemic mixture of propoxy analog at the twelfth carbon. FD25 is a racemic butoxy mixture at the twelfth carbon of AS56. AS61 is saturated at the ninth carbon of AS56. The effects of the EpOME analogs were assessed on two cellular immune responses: hemocyte-spreading and nodule formation. All four analogs inhibited the cellular immune responses; however, AS56 was the most potent in inhibiting the immune responses. FD25 and AS61 were significantly less potent compared to AS56, suggesting crucial roles of the double bond at the ninth carbon and the propoxy chain at the twelfth carbon. The stronger inhibitory activity of AS56 compared to PD28 also suggests the functional role of the stereoisomeric form in physiological functions. The cytotoxicity of AS56 was also the most potent among the analogs, suggesting its insecticidal activity. Subsequent insecticidal bioassays on AS56 toxicity were performed against different insect species. These EpOME analogs were potent against lepidopteran insects (S. exigua and Plutella xylostella) but not against coleopteran (Tenebrio molitor) or thysanopteran (Frankliniella occidentalis) species. Among the EpOME analogs, AS56 was the most toxic against the lepidopteran insects. Spraying AS56 in cabbage fields infested by lepidopteran insects led to acute and high control efficacy against two lepidopteran pests, similar to that of a chemical insecticide, fluxametamide. The AS56-intoxicated larvae exhibited over-excitation in their behavior around 12 h post-treatment. This study indicates that AS56 exhibits an oral toxicity against lepidopteran insects with its cytotoxicity and behavioral over-excitation.