Olean-18-ene triterpenoids from Celastraceae species inhibit HIV replication targeting NF-kB and Sp1 dependent transcription

Eur J Med Chem. 2012 Jun;52:295-303. doi: 10.1016/j.ejmech.2012.03.035. Epub 2012 Mar 28.

Abstract

In the present study we report the isolation of nine new olean-18-ene triterpenes (1-9), along with three known ones (10-12), from Cassine xylocarpa and Maytenus jelskii. Their stereostructures have been elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR techniques (COSY, ROESY, HSQC and HMBC), and spectrometric methods. The natural compounds and derivatives 13-15 have been tested for their potential as inhibitors of human immunodeficiency virus type 1 replication. Five compounds from this series displayed potent antiviral activity with IC(50)s in the micromolar range (1, 3, 4, 7 and 8) being 1 and 8 the most active compounds. The target of these compounds was different from antiretroviral drugs currently licensed as they act as inhibitors of enhancer-dependent transcription. The structure-activity relationships were established based on the regiosubstitution and oxidation degree of the triterpene scaffold, revealing that these aspects were able to modulate the selectivity and intensity of HIV inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / toxicity
  • Biological Products / pharmacology
  • Biological Products / toxicity
  • Celastraceae / chemistry*
  • Cell Line
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • HIV-1 / physiology
  • Lymphocytes / drug effects
  • Lymphocytes / virology
  • Models, Molecular
  • Molecular Conformation
  • NF-kappa B / metabolism*
  • Sp1 Transcription Factor / metabolism*
  • Structure-Activity Relationship
  • Terpenes / chemical synthesis
  • Terpenes / chemistry
  • Terpenes / pharmacology*
  • Terpenes / toxicity
  • Transcription, Genetic / drug effects*
  • Virus Replication / drug effects*

Substances

  • Anti-HIV Agents
  • Biological Products
  • NF-kappa B
  • Sp1 Transcription Factor
  • Terpenes