Discovery and Characterization of 2-Nitro-5-(4-(phenylsulfonyl)piperazin-1-yl)- N-(pyridin-4-ylmethyl)anilines as Novel Inhibitors of the Aedes aegypti Kir1 (AeKir1) Channel

Christopher D. Aretz, M. Jane Morwitzer, Austin G. Sanford, Alicia M. Hogan, Madelene V. Portillo, Sujay V. Kharade, Meghan Kramer, James B. McCarthey, Renata Rusconi Trigueros, Peter M. Piermarini, Jerod S. Denton, Corey R. Hopkins

Research output: Contribution to journalArticle

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-4-ylmethyl)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.

Original languageEnglish (US)
Pages (from-to)917-931
Number of pages15
JournalACS infectious diseases
Volume5
Issue number6
DOIs
StatePublished - Jun 14 2019

Keywords

  • Aedes aegypti
  • Kir channels
  • Zika
  • larvae
  • vector-borne diseases

ASJC Scopus subject areas

  • Infectious Diseases

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