| Abstract
| - Parasite resistance to drugs has emerged as a major problem in current medicine, and therefore,there is great clinical interest in developing compounds that overcome these resistances. In anintensive study of South American medicinal plants, herein we report the isolation, structureelucidation, and biological activity of dihydro-β-agarofuran sesquiterpenes from the roots ofMaytenus magellanica (1−14) and M. chubutensis (14−17). This type of natural products maybe considered as privileged structures. The structures of 10 new compounds, 1, 3, 6−9, and12−15, were determined by means of 1H and 13C NMR spectroscopic studies, includinghomonuclear (COSY and ROESY) and heteronuclear correlation experiments (HMQC andHMBC). The absolute configurations of eight hetero- and homochromophoric compounds, 1, 3,6−9, 12, and 13, were determined by means of CD studies. Fourteen compounds, 1−3 and6−16, have been tested on a multidrug-resistant Leishmania tropica line overexpressing aP-glycoprotein-like transporter to determine their ability to revert the resistance phenotypeand to modulate intracellular drug accumulation. From this series, 1, 2, 3, 14, and 15 showedpotent activity, 1 being the most active compound. The structure−activity relationships of thedifferent compounds are discussed.
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