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

Bioorg Med Chem. 2016 Nov 1;24(21):5618-5625. doi: 10.1016/j.bmc.2016.09.028. Epub 2016 Sep 12.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • HEK293 Cells
  • HIV-1 / drug effects*
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Nuclear Matrix / drug effects
  • Quinolines / chemical synthesis
  • Quinolines / chemistry
  • Quinolines / pharmacology*
  • RNA, Viral / antagonists & inhibitors
  • Structure-Activity Relationship

Substances

  • Anti-HIV Agents
  • Quinolines
  • RNA, Viral