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Further SAR on the (Phenylsulfonyl)piperazine Scaffold as Inhibitors of the Aedes aegypti Kir1 ( Ae Kir) Channel and Larvicides
Author(s) -
Aretz Christopher D.,
Kharade Sujay V.,
Chronister Keagan,
Rusconi Trigueros Renata,
Martinez Rodriguez Erick J.,
Piermarini Peter M.,
Denton Jerod S.,
Hopkins Corey R.
Publication year - 2021
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202000598
Subject(s) - aedes aegypti , chikungunya , aedes , biology , zika virus , dengue fever , yellow fever , arbovirus , toxicology , dengue virus , vector (molecular biology) , mosquito control , larva , virology , pharmacology , virus , malaria , ecology , immunology , genetics , gene , recombinant dna
Zika virus (ZIKV), dengue fever (DENV) and chikungunya (CHIKV) are arboviruses that are spread to humans from the bite of an infected adult female Aedes aegypti mosquito. As there are no effective vaccines or therapeutics for these diseases, the primary strategy for controlling the spread of these viruses is to prevent the mosquito from biting humans through the use of insecticides. Unfortunately, the commonly used classes of insecticides have seen a significant increase in resistance, thus complicating control efforts. Inhibiting the renal inward rectifier potassium (Kir) channel of the mosquito vector Aedes aegypti has been shown to be a promising target for the development of novel mosquitocides. We have shown that Kir1 channels play key roles in mosquito diuresis, hemolymph potassium homeostasis, flight, and reproduction. Previous work from our laboratories identified a novel (phenylsulfonyl)piperazine scaffold as potent Ae Kir channel inhibitors with activity against both adult and larval mosquitoes. Herein, we report further SAR work around this scaffold and have identified additional compounds with improved in vitro potency and mosquito larvae toxicity.