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

Abstract

The effects produced by nine dihydro-β-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 1H-13C 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.