Phylobioactive hotspots in plant resources used to treat Chagas disease.

Globally, more than six million people are infected with Trypanosoma cruzi, the causative protozoan parasite of the vector-borne Chagas disease (CD). We conducted a cross-sectional ethnopharmacological field study in Bolivia among different ethnic groups where CD is hyperendemic. A total of 775 extracts of botanical drugs used in Bolivia in the context of CD and botanical drugs from unrelated indications from the Mediterranean De Materia Medica compiled by Dioscorides two thousand years ago were profiled in a multidimensional assay uncovering different antichagasic natural product classes. Intriguingly, the phylobioactive anthraquinone hotspot matched the antichagasic activity of Senna chloroclada, the taxon with the strongest ethnomedical consensus for treating CD among the Izoceño-Guaraní. Testing common 9,10-anthracenedione derivatives in T. cruzi cellular infection assays demarcates hydroxyanthraquinone as a potential antichagasic lead scaffold. Our study systematically uncovers in vitro antichagasic phylogenetic hotspots in the plant kingdom as a potential resource for drug discovery based on ethnopharmacological hypotheses.

New cycloartane-type ester triterpenes from Euphorbia pterococca and biological evaluation.

From acetonic extract of the whole plant Euphorbia pterococca Brot. (Euphorbiaceae), four new cycloartane-type ester triterpenes named cycloartenyl-2'E,4'E-decadienoate (1), cycloartenyl-2'E,4'Z-decadienoate (2), 24-methylenecycloartanyl-2'E,4'Z-tetradecadienoate (3), and 24-oxo-29-norcycloartanyl-2'E,4'Z-hexadecadienoate (4) were obtained along with nine known tetracyclic triterpenes (5-13). Their structures were established mainly by extensive use of spectroscopic techniques, including 1D (1H and 13C) and 2D homo- and heteronuclear NMR experiments (COSY, HSQC, HMBC and NOESY), and mass spectrometry (HRESIMS), and by comparison with data reported in the literature. In addition, the new compounds 1-3 have been tested for cytotoxicity, trypanocidal effects and on enzymes involved in endocannabinoid degradation. While inactive in all assays up to 100 µM, 1 showed selective inhibition of α/ß-hydrolase 12 with an IC50 of 11.6 ±â€¯1.9 µM.