Aretz Christopher D, Morwitzer M Jane, Sanford Austin G, Hogan Alicia M, Portillo Madelene V, Kharade Sujay V, Kramer Meghan, McCarthey James B, Trigueros Renata Rusconi, Piermarini Peter M, Denton Jerod S, Hopkins Corey R
Department of Anesthesiology , Vanderbilt University Medical Center , Nashville , Tennessee 37232 , United States.
Department of Entomology , Ohio State University , Wooster , Ohio 44691 , United States.
ACS Infect Dis. 2019 Jun 14;5(6):917-931. doi: 10.1021/acsinfecdis.8b00368. Epub 2019 Mar 15.
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.
寨卡病毒、登革热和基孔肯雅热等蚊媒虫媒病毒疾病通过受感染的成年雌性埃及伊蚊传播给人类，影响着世界上很大一部分人口。埃及伊蚊中的Kir1通道（AeKir1）是蚊子马氏（肾）小管功能中的一个重要离子通道，并且是一个可以被操纵以破坏蚊子排泄功能的通道。我们之前报道了发现各种对AeKir1通道有活性的支架。在此，我们报道一种新型2-硝基-5-(4-(苯基磺酰基)哌嗪-1-基)-N-(吡啶-4-基甲基)苯胺支架作为AeKir1抑制剂的合成及生物学特性。与之前报道的支架相比，这种新型支架在体外更有效，并且这些分子能杀死蚊虫幼虫。
