Antitrypanosomal Lactones from Nectandra barbellata

Twigs of Nectandra barbellata were extracted using a solution of the ionic liquid 1-butyl-3-methylimidazolium bromide (BMImBr) in H2O, assisted by microwave (MAE). After successive chromatographic steps, one sesquiterpene, costic acid, and three new related lactones, (R)-3­(7)-Z-3-hexadec-21-enylidene-5-(hydroxymethyl)­tetrahydrofuran-2-one (1), (R)-3­(7)-Z-3-hexadecylidene-5-(hydroxymethyl)­tetrahydrofuran-2-one (2), and (R)-3­(7)-Z-3-docosylidene-5-(hydroxymethyl)­tetrahydrofuran-2-one (3), were isolated. After structural elucidation using IR, UV, HRESIMS, NMR, ECD, and VCD, compounds 1–3 were tested against trypomastigote forms of Trypanosoma cruzi. The mechanism of action of bioactive isolated compounds was studied using different fluorescent-based approaches to investigate alterations of the plasma membrane, permeability/electric potential (ΔΨp), reactive oxygen species levels, mitochondria (electric membrane potential, ΔΨm/ATP levels), Ca2+ levels, and pH of the acidocalcisomes. In addition, in silico studies predicted no resemblance to pan assay interference compounds (PAINS).