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

The effects produced by nine dihydro-beta-agarofuran sesquiterpenes isolate d from Crossopetalum tonduzii (1-8) and Maytenus macrocarpa (9) (Celastrace ae) on the reversion of the resistant phenotype on a multidrug-resistant Le ishmania line and their binding to recombinant C-terminal nucleotide-bindin g domain of Leishmania P-glycoprotein-like transporter were studied. The st ructures of the new compounds (1-5) were elucidated by spectroscopic method s, including H-1-C-13 heteronuclear correlation (HMQC), long-range correlat ion 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.