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

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 CC50 values 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 languageEnglish (US)
Pages (from-to)5618-5625
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume24
Issue number21
DOIs
StatePublished - Nov 1 2016

Fingerprint

Cytotoxicity
HIV-1
Viruses
Proteins
Crosslinking
Glutathione
Assays
Vaccines
Inactivated Vaccines
RNA
Virion
Therapeutics

Keywords

  • HIV
  • Quinolinequinone
  • Virus

ASJC Scopus subject areas

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

Cite this

Analysis of quinolinequinone reactivity, cytotoxicity, and anti-HIV-1 properties. / Alfadhli, Ayna; Mack, Andrew; Harper, Logan; Berk, Sam; Ritchie, Christopher; Barklis, Eric.

In: Bioorganic and Medicinal Chemistry, Vol. 24, No. 21, 01.11.2016, p. 5618-5625.

Research output: Contribution to journalArticle

Alfadhli, Ayna ; Mack, Andrew ; Harper, Logan ; Berk, Sam ; Ritchie, Christopher ; Barklis, Eric. / Analysis of quinolinequinone reactivity, cytotoxicity, and anti-HIV-1 properties. In: Bioorganic and Medicinal Chemistry. 2016 ; Vol. 24, No. 21. pp. 5618-5625.
@article{488c2ff68d11446d996bd3b5e716efbd,
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 CC50 values 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.",
keywords = "HIV, Quinolinequinone, Virus",
author = "Ayna Alfadhli and Andrew Mack and Logan Harper and Sam Berk and Christopher Ritchie and Eric Barklis",
year = "2016",
month = "11",
day = "1",
doi = "10.1016/j.bmc.2016.09.028",
language = "English (US)",
volume = "24",
pages = "5618--5625",
journal = "Bioorganic and Medicinal Chemistry",
issn = "0968-0896",
publisher = "Elsevier Limited",
number = "21",

}

TY - JOUR

T1 - Analysis of quinolinequinone reactivity, cytotoxicity, and anti-HIV-1 properties

AU - Alfadhli, Ayna

AU - Mack, Andrew

AU - Harper, Logan

AU - Berk, Sam

AU - Ritchie, Christopher

AU - Barklis, Eric

PY - 2016/11/1

Y1 - 2016/11/1

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 CC50 values 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 CC50 values 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.

KW - HIV

KW - Quinolinequinone

KW - Virus

UR - http://www.scopus.com/inward/record.url?scp=84991734958&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84991734958&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2016.09.028

DO - 10.1016/j.bmc.2016.09.028

M3 - Article

VL - 24

SP - 5618

EP - 5625

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

SN - 0968-0896

IS - 21

ER -