New natural sesquiterpenes as modulators of daunomycin resistance in a multidrug-resistant Leishmania tropica line

J Med Chem. 1999 Oct 21;42(21):4388-93. doi: 10.1021/jm991066b.

Abstract

The effects produced by nine dihydro-beta-agarofuran sesquiterpenes isolated from Crossopetalum tonduzii (1-8) and Maytenus macrocarpa (9) (Celastraceae) on the reversion of the resistant phenotype on a multidrug-resistant Leishmania line and their binding to recombinant C-terminal nucleotide-binding domain of Leishmania P-glycoprotein-like transporter were studied. The structures of the new compounds (1-5) were elucidated by spectroscopic methods, including (1)H-(13)C heteronuclear correlation (HMQC), long-range correlation spectra with inversal detection (HMBC), ROESY experiments, and chemical correlations. The absolute configuration of one of them (1) was determined by CD studies. The structure-activity relationship is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Animals
  • Antibiotics, Antineoplastic / pharmacology*
  • Circular Dichroism
  • Daunorubicin / pharmacology*
  • Drug Resistance, Multiple
  • Escherichia coli / metabolism
  • Leishmania tropica / drug effects*
  • Leishmania tropica / metabolism
  • Protein Binding
  • Rosales / chemistry*
  • Sesquiterpenes / chemical synthesis*
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / metabolism
  • Sesquiterpenes / pharmacology
  • Structure-Activity Relationship
  • Trypanocidal Agents / chemical synthesis*
  • Trypanocidal Agents / chemistry
  • Trypanocidal Agents / metabolism
  • Trypanocidal Agents / pharmacology

Substances

  • 8-acetoxy-9-benzoyloxy-15(2)-methylbutyroyloxy-2-nicotynoyloxy-1,4,6-trihydroxydihydro-beta-agarofuran
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antibiotics, Antineoplastic
  • Sesquiterpenes
  • Trypanocidal Agents
  • Daunorubicin