Analysis of quinolinequinone reactivity, cytotoxicity, and anti-HIV-1 properties

Ayna Alfadhli; Andrew Mack; Logan Harper; Sam Berk; Christopher Ritchie; Eric Barklis

doi:10.1016/j.bmc.2016.09.028

Analysis of quinolinequinone reactivity, cytotoxicity, and anti-HIV-1 properties

Ayna Alfadhli, Andrew Mack, Logan Harper, Sam Berk, Christopher Ritchie, Eric Barklis

Molecular Microbiology and Immunology

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

17 Scopus citations

Abstract

We have analyzed a set of quinolinequinones with respect to their reactivities, cytotoxicities, and anti-HIV-1 properties. Most of the quinolinequinones were reactive with glutathione, and several acted as sulfhydryl crosslinking agents. Quinolinequinones inhibited binding of the HIV-1 matrix protein to RNA to varying degrees, and several quinolinequinones showed the capacity to crosslink HIV-1 matrix proteins in vitro, and HIV-1 structural proteins in virus particles. Cytotoxicity assays yielded quinolinequinone CC₅₀values in the low micromolar range, reducing the potential therapeutic value of these compounds. However, one compound, 6,7-dichloro-5,8-quinolinequinone potently inactivated HIV-1, suggesting that quinolinequinones may prove useful in the preparation of inactivated virus vaccines or for other virucidal purposes.

Original language	English (US)
Pages (from-to)	5618-5625
Number of pages	8
Journal	Bioorganic and Medicinal Chemistry
Volume	24
Issue number	21
DOIs	https://doi.org/10.1016/j.bmc.2016.09.028
State	Published - 2016

Keywords

HIV
Quinolinequinone
Virus

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmc.2016.09.028

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title = "Analysis of quinolinequinone reactivity, cytotoxicity, and anti-HIV-1 properties",

abstract = "We have analyzed a set of quinolinequinones with respect to their reactivities, cytotoxicities, and anti-HIV-1 properties. Most of the quinolinequinones were reactive with glutathione, and several acted as sulfhydryl crosslinking agents. Quinolinequinones inhibited binding of the HIV-1 matrix protein to RNA to varying degrees, and several quinolinequinones showed the capacity to crosslink HIV-1 matrix proteins in vitro, and HIV-1 structural proteins in virus particles. Cytotoxicity assays yielded quinolinequinone CC50values in the low micromolar range, reducing the potential therapeutic value of these compounds. However, one compound, 6,7-dichloro-5,8-quinolinequinone potently inactivated HIV-1, suggesting that quinolinequinones may prove useful in the preparation of inactivated virus vaccines or for other virucidal purposes.",

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AU - Mack, Andrew

AU - Harper, Logan

AU - Berk, Sam

AU - Ritchie, Christopher

AU - Barklis, Eric

PY - 2016

Y1 - 2016

N2 - We have analyzed a set of quinolinequinones with respect to their reactivities, cytotoxicities, and anti-HIV-1 properties. Most of the quinolinequinones were reactive with glutathione, and several acted as sulfhydryl crosslinking agents. Quinolinequinones inhibited binding of the HIV-1 matrix protein to RNA to varying degrees, and several quinolinequinones showed the capacity to crosslink HIV-1 matrix proteins in vitro, and HIV-1 structural proteins in virus particles. Cytotoxicity assays yielded quinolinequinone CC50values in the low micromolar range, reducing the potential therapeutic value of these compounds. However, one compound, 6,7-dichloro-5,8-quinolinequinone potently inactivated HIV-1, suggesting that quinolinequinones may prove useful in the preparation of inactivated virus vaccines or for other virucidal purposes.

AB - We have analyzed a set of quinolinequinones with respect to their reactivities, cytotoxicities, and anti-HIV-1 properties. Most of the quinolinequinones were reactive with glutathione, and several acted as sulfhydryl crosslinking agents. Quinolinequinones inhibited binding of the HIV-1 matrix protein to RNA to varying degrees, and several quinolinequinones showed the capacity to crosslink HIV-1 matrix proteins in vitro, and HIV-1 structural proteins in virus particles. Cytotoxicity assays yielded quinolinequinone CC50values in the low micromolar range, reducing the potential therapeutic value of these compounds. However, one compound, 6,7-dichloro-5,8-quinolinequinone potently inactivated HIV-1, suggesting that quinolinequinones may prove useful in the preparation of inactivated virus vaccines or for other virucidal purposes.

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Analysis of quinolinequinone reactivity, cytotoxicity, and anti-HIV-1 properties

Abstract

Keywords

ASJC Scopus subject areas

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