Prostratin and 12-O-tetradecanoylphorbol 13-acetate are potent and selective inhibitors of Chikungunya virus replication

J Nat Prod. 2012 Dec 28;75(12):2183-7. doi: 10.1021/np300637t. Epub 2012 Dec 7.

Abstract

A chemical study of the Vietnamese plant species Trigonostemon howii led to the isolation of a new tigliane-type diterpenoid, trigowiin A (1), along with several known coumarins and phenylpropanoids. The planar structure and the relative configuration of compound 1 were elucidated based on spectroscopic analysis, including 1D- and 2D-NMR experiments, mass spectrometry, and comparison with literature data. Trigowiin A (1) exhibited moderate antiviral activity in a virus-cell-based assay for Chikungunya virus (CHIKV). Since the structure of compound 1 is closely related to those of well-known tigliane diterpenoids such as prostratin (2), phorbol (3), 12-O-tetradecanoylphorbol 13-acetate (TPA) (4), and 4α-TPA (5), the antiviral activity of the latter compounds was also evaluated against CHIKV, as well as in virus-cell-based assays of two additional members of the genus Alphavirus (Sindbis virus, SINV, and Semliki forest virus, SFV). Whereas prostratin inhibited CHIKV replication with a moderate EC(50) of 2.6 μM and a selectivity index (SI) approximating 30, compound 4 proved to be an extremely potent inhibitor, with an EC(50) of ∼3 nM and a SI near 2000. Interestingly, no or very little activity was observed on the replication of SINV and SFV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemistry
  • Antiviral Agents / isolation & purification*
  • Antiviral Agents / pharmacology*
  • Chikungunya virus / drug effects*
  • Diterpenes / chemistry
  • Diterpenes / isolation & purification
  • Diterpenes / pharmacology*
  • Euphorbiaceae / chemistry*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Phorbol Esters / chemistry
  • Phorbol Esters / pharmacology*
  • Plant Bark / chemistry
  • Tetradecanoylphorbol Acetate / pharmacology*
  • Vietnam

Substances

  • Antiviral Agents
  • Diterpenes
  • Phorbol Esters
  • trigowiin A
  • prostratin
  • Tetradecanoylphorbol Acetate