Characterization of Toxicological and Neurophysiological Effects of Natural Product Based Chromenes to Fall Armyworm, Spodoptera frugiperda.

We previously extracted and purified a chromene amide from Amyris texana and found this scaffold is moderately insecticidal and thus, this study aimed to test the insecticidal properties of 13 synthetically derived chromene analogs to the fall armyworm (FAW, Spodoptera frugiperda). Microinjection of chromenes with alcohol or aldehydes substitutions at the meta position on the benzopyran moiety led to moderate toxicity that was approximately 2- to 3-fold less toxic when compared to permethrin, yet microinjection of differently substituted chromenes exhibited little to no toxicity. Similarly, chromenes with alcohol or aldehydes substitutions at the meta position on the benzopyran moiety were among the most toxic chromenes studied through ingested exposure. In addition to acute toxicity, select chromenes significantly increased the percentage of developmental defects upon eclosion that prevented adult moths from being capable of flight, suggesting these compounds alter development. Interestingly, microinjection yielded differing signs of intoxication between alcohol and aldehyde substitutions where the alcohol resulted in flaccid paralysis and lethargy whereas aldehyde led to tonic contractions and hyperactivity. These contrasting signs of intoxication were also observed in electrophysiological assays where alcohol substitutions led to the depression of central neuron firing activity and aldehyde substitutions led to hyperexcitation of central neurons. In summary, the chromene amides led to acute lethality and/or altered developmental trajectories of FAW, yet the high doses required for acute mortality suggest these scaffolds hold relatively little promise for development into FAW-directed insecticides but may represent novel growth regulators for FAW.