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

doi:10.1021/acsinfecdis.8b00368

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 journal › Article › peer-review

6 Scopus citations

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 language	English (US)
Pages (from-to)	917-931
Number of pages	15
Journal	ACS infectious diseases
Volume	5
Issue number	6
DOIs	https://doi.org/10.1021/acsinfecdis.8b00368
State	Published - Jun 14 2019

Keywords

Aedes aegypti
Kir channels
Zika
larvae
vector-borne diseases

ASJC Scopus subject areas

Infectious Diseases

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10.1021/acsinfecdis.8b00368

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Aretz, C. D., Morwitzer, M. J., Sanford, A. G., Hogan, A. M., Portillo, M. V., Kharade, S. V., Kramer, M., McCarthey, J. B., Trigueros, R. R., Piermarini, P. M., Denton, J. S., & Hopkins, C. R. (2019). 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. ACS infectious diseases, 5(6), 917-931. https://doi.org/10.1021/acsinfecdis.8b00368

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. / Aretz, Christopher D.; Morwitzer, M. Jane; Sanford, Austin G. et al.
In: ACS infectious diseases, Vol. 5, No. 6, 14.06.2019, p. 917-931.

Research output: Contribution to journal › Article › peer-review

Aretz, CD, Morwitzer, MJ, Sanford, AG, Hogan, AM, Portillo, MV, Kharade, SV, Kramer, M, McCarthey, JB, Trigueros, RR, Piermarini, PM, Denton, JS & Hopkins, CR 2019, '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', ACS infectious diseases, vol. 5, no. 6, pp. 917-931. https://doi.org/10.1021/acsinfecdis.8b00368

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title = "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",

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.",

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AU - Morwitzer, M. Jane

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AU - Hogan, Alicia M.

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AU - Kharade, Sujay V.

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AU - McCarthey, James B.

AU - Trigueros, Renata Rusconi

AU - Piermarini, Peter M.

AU - Denton, Jerod S.

AU - Hopkins, Corey R.

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N2 - 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.

AB - 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.

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KW - vector-borne diseases

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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

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