Synthesis and trypanocidal activity of ent-kaurane glycosides

Bioorg Med Chem. 2007 Jan 1;15(1):381-91. doi: 10.1016/j.bmc.2006.09.048. Epub 2006 Oct 20.

Abstract

Novel ent-kaurane glucosides were synthezised by a Koenigs-Knorr reaction between C17 and C19 alcohols derived from kaurenoic acid and 2,3,4,6-tetra-O-acetyl-glucopyranosyl bromide, followed by the hydrolysis of the acetates. Main products were assayed in vitro and in vivo against blood trypomastigote forms of Trypanosoma cruzi, the aetiological agent of Chagas' disease (American trypanosomiasis). The results allowed to establish structure-activity relationships among these derivatives, as well as pointed out the C19-methylester-C17-O-glucoside as a potential trypanocidal agent, whose trypanocidal profile was shown to be comparable to those of gentian violet and benznidazole.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Diterpenes, Kaurane / chemical synthesis*
  • Diterpenes, Kaurane / chemistry
  • Diterpenes, Kaurane / pharmacology*
  • Glycosides / chemical synthesis*
  • Glycosides / chemistry
  • Glycosides / pharmacology*
  • Male
  • Mice
  • Molecular Conformation
  • Parasitic Sensitivity Tests
  • Stereoisomerism
  • Structure-Activity Relationship
  • Trypanocidal Agents / chemical synthesis*
  • Trypanocidal Agents / chemistry
  • Trypanocidal Agents / pharmacology*
  • Trypanosoma cruzi / drug effects

Substances

  • Diterpenes, Kaurane
  • Glycosides
  • Trypanocidal Agents