Analysis of quinolinequinone reactivity, cytotoxicity, and anti-HIV-1 properties.
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.
Oregon Health & Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, United States.
Ayna
A
Alfadhli
Oregon Health & Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, United States.
Andrew
A
Mack
Oregon Health & Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, United States.
Logan
L
Harper
Oregon Health & Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, United States.
Sam
S
Berk
Oregon Health & Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, United States.
Christopher
C
Ritchie
Oregon Health & Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, United States. Electronic address: barklis@ohsu.edu.
Eric
E
Barklis
D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D015530:Nuclear Matrix / Q000187:drug effects; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012367:RNA, Viral / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D011804:Quinolines; D012367:RNA, Viral
HIV; Quinolinequinone; Virus
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