Neoflavonoids as Inhibitors of HIV-1 Replication by Targeting the Tat and NF-κB Pathways

Molecules. 2017 Feb 19;22(2):321. doi: 10.3390/molecules22020321.

Abstract

Twenty-eight neoflavonoids have been prepared and evaluated in vitro against HIV-1. Antiviral activity was assessed on MT-2 cells infected with viral clones carrying the luciferase reporter gene. Inhibition of HIV transcription and Tat function were tested on cells stably transfected with the HIV-LTR and Tat protein. Seven 4-phenylchromen-2-one derivatives showed HIV transcriptional inhibitory activity but only the phenylchrome-2-one 10 inhibited NF-κB and displayed anti-Tat activity simultaneously. Compounds 10, 14, and 25, inhibited HIV replication in both targets at concentrations <25 μM. The assays of these synthetic 4-phenylchromen-2-ones may aid in the investigation of some aspects of the anti-HIV activity of such compounds and could serve as a scaffold for designing better anti-HIV compounds, which may lead to a potential anti-HIV therapeutic drug.

Keywords: 4-phenyl-chromen-one; AIDS; NF-κB inhibition; Tat protein; anti-HIV activity; neoflavonoids.

MeSH terms

  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / isolation & purification
  • Anti-HIV Agents / pharmacology*
  • Flavonoids / chemistry
  • Flavonoids / isolation & purification
  • Flavonoids / pharmacology*
  • HIV Infections / drug therapy
  • HIV Infections / metabolism
  • HIV Infections / virology
  • HIV-1 / drug effects*
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Structure
  • NF-kappa B / metabolism*
  • Signal Transduction / drug effects*
  • Virus Replication / drug effects
  • tat Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

  • Anti-HIV Agents
  • Flavonoids
  • NF-kappa B
  • tat Gene Products, Human Immunodeficiency Virus