Quassinoids: Viral protein R inhibitors from Picrasma javanica bark collected in Myanmar for HIV infection

Bioorg Med Chem Lett. 2016 Oct 1;26(19):4620-4624. doi: 10.1016/j.bmcl.2016.08.055. Epub 2016 Aug 21.

Abstract

Viral protein R (Vpr) is an accessory protein that plays important roles in the viral pathogenesis of Human Immunodeficiency Virus-1 (HIV-1). An assay for anti-Vpr activity, using TREx-HeLa-Vpr cells, is a promising strategy to discover Vpr inhibitors. The anti-Vpr assay revealed that the CHCl3-soluble extract of Picrasma javanica bark possesses potent anti-Vpr activity. Furthermore, studies of quassinoids (1-15) previously isolated from the extract demonstrated that all of the tested quassinoids exhibit anti-Vpr activity. Among the tested compounds, javanicin I (15) exhibited the most potent anti-Vpr activity ((***)p <0.001) in comparing with that of the positive control, damnacanthal. The structure-activity relationships of the active quassinoids suggested that the presence of a methyl group at C-13 in the 2,12,14-triene-1,11,16-trione-2,12-dimethoxy-18-norpicrasane quassinoids is the important factor for the potent inhibitory effect in TREx-HeLa-Vpr cells.

Keywords: Picrajavanicins; Picrasma javanica; Quassinoids; Structure–activity relationships; Viral protein R inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / therapeutic use*
  • Gene Products, vpr / antagonists & inhibitors*
  • HIV Infections / drug therapy*
  • HeLa Cells
  • Humans
  • Myanmar
  • Picrasma / chemistry*
  • Plant Bark / chemistry*
  • Quassins / chemistry
  • Quassins / pharmacology*
  • Structure-Activity Relationship

Substances

  • Anti-HIV Agents
  • Gene Products, vpr
  • Quassins