Background: The adrenergic mode of action was investigated for the development of potential new insecticides. Clonidine-related analogs were tested against Myzus persicae (Sulzer) and Bemisia tabaci (Gennadius). Clonidine analogs lack translation owing to a possible vacuole-trapping mechanism. Physical property modulation via a prodrug approach was attempted to overcome this mechanism.
Results: Clonidine showed insecticidal activity against M. persicae and B. tabaci. A prodrug of a known open-chain analog of clonidine was developed. While the prodrug had decreased pKa and increased lipophilicity and displayed good activity against M. persicae B. tabaci, the activity did not translate to cotton. Metabolic studies showed that the prodrug was quickly metabolized to the parent compound, and was further metabolized to a known vacuole-trapped oxazoline analog.
Conclusions: Adrenergic active compounds, such as clonidine analogs, show potential as insecticides; however, a designed prodrug approach did not overcome the lack of translation in this case. Studies confirmed that the synthesized prodrug analog metabolized in planta to the proposed vacuole-trapped compound. One possible explanation for the failure of this approach is that the rate of metabolism and vacuole trapping is faster than translaminar flow, and therefore the released pesticide is not biologically available to the target organism. © 2016 Society of Chemical Industry.
Keywords: adrenergic; green peach aphid; metabolism; prodrug; translaminar; vacuole trapping; whitefly.
© 2016 Society of Chemical Industry.