No abstract

Mosquito-borne arboviral diseases such as Zika, dengue fever and chikungunya are transmitted to humans by infected adult female Aedes aegypti mosquitoes and affect a large portion of the world's population. The Kir1 channel in Ae. aegypti (AeKir1) is an important ion channel in the functioning of mosquito Malpighian (renal) tubules and one that can be manipulated in order to disrupt excretory functions in mosquitoes. We have previously reported the discovery of various scaffolds that are active against the AeKir1 channel. Herein we report the synthesis and biological characterization of a new 2-nitro-5-(4-(phenylsulfonyl) piperazin-1-yl)-N-(pyridin-4ylmethyl)anilines scaffold as inhibitors of AeKir1. This new scaffold is more potent in vitro compared to the previously reported scaffolds, and the molecules kill mosquito larvae.

Vector‐borne diseases such as Zika virus, dengue fever and chikungunya virus are transmitted by infected Aedes aegypti female mosquitoes and affect a large portion of the world's population. The use of neurotoxic insecticides to reduce mosquito populations has led to the emergence of genetically resistant strains of mosquitoes over the last several decades, prompting us to explore other physiological targets that might be suitable for insecticide development. Inward rectifier potassium (Kir) channels play essential roles in the physiology of the mosquito Malpighian (renal) tubule and represent “druggable” targets that can be exploited to inhibit renal excretory function. We have previously reported on the discovery of various scaffolds that are active against the Aedes aegypti Kir1 (AeKir1) channel. Herein we report the synthesis and biological characterization of a new 2‐nitro‐5‐(4‐(phenylsulfonyl) piperazin‐1‐yl)‐N‐(pyridin‐4‐ylmethyl)anilines scaffold as an inhibitor of the AeKir1 channel. This new scaffold is more potent in vitro compared to the previously reported scaffolds, in addition, the molecules kill mosquito larvae.Support or Funding InformationThis work is funded by National Institutes of Health grant 1R21 AI128418‐01A1.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.