Voltage-Sensitive Potassium Kv2 Channels as New Targets for Insecticides

The diacylhydrazines are a class of insecticides usually thought to act by disrupting the insect endocrine system. However, at field use rates, insects affected by these compounds also show signs of neurotoxicity. Previous research found that a blocking action on Kv2 potassium channels of nerve and muscle was the cause of the observed neurotoxicity. This review will summarize the physiological role of Kv2 channels and their possible exploitation as a new target for insecticide development. Included is a description of a potassium channel homology model to visualize protein structures of mosquito and human, and to facilitate design of molecules that are safe and effective. Also included is a proposed ligand docking example with a substituted catechol as a model potassium channel blocker. Preliminary toxicity studies demonstrate that molecules of this type show greater acute toxicity to mosquitoes than the diacylhydrazines. The overall aim of this project is a new commercial insecticide for use in the fight against global malaria. (C) 2014 American Chemical Society.