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
N1 - Funding Information:
We are grateful to Dr. Dennis Koop and the OHSU Bioanalytical Shared Resource Pharmacokinetics Core for help with the MS analysis, to the Oregon Translational Research and Drug Development Institute (OTRADI) for assistance and financial support, and to the NIH for support through grants R01 GM060170 and R01 GM101983 .
Publisher Copyright:
© 2016 Elsevier Ltd
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.
KW - HIV
KW - Quinolinequinone
KW - Virus
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U2 - 10.1016/j.bmc.2016.09.028
DO - 10.1016/j.bmc.2016.09.028
M3 - Article
C2 - 27663546
AN - SCOPUS:84991734958
SN - 0968-0896
VL - 24
SP - 5618
EP - 5625
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 21
ER -