Isolation and chacarterization of a new anti-trypanosomal guanidine alkaloid from Alchornea glandulosa (Euphorbiaceae)

Bioactivity-guided fractionation of MeOH extract from leaves of Alchornea glandulosa Poepp. (Euphorbiaceae) afforded a new guanidine alkaloid named alchornedine. Its structure, which displayed a very rare ring system, was elucidated based on NMR, IR and MS spectral analysis. Alchornedine displayed an antiprotozoal activity against Trypanosoma cruzi (Y strain). By using the MTT assay, the trypomastigotes showed an IC₅₀ value of 92.54 µg/mL (442.8µM), a similar effectiveness to the standard drug benznidazole. Alchornedine showed a promising activity against the intracellular amastigotes, with an IC₅₀ value of 27.17 µg/mL (129.1µM). Considering benznidazole as standard drug, this guanidine alkaloid was approximately 3-fold more effective against the intracellular form of T. cruzi. The mammalian cytotoxicity of alchornedine was verified against NCTC cells and demonstrated an IC₅₀ of 49.62 µg/mL (237.4µM), but the compound demonstrated a selective elimination of parasites inside macrophages, without affecting the morphology of host cells. Alchornedine was effective against both clinical forms of T. cruzi and could be used as a scaffold for future drug design studies against American Trypanosomiais.

Keywords: Alchornea glandulosa, Euphorbiaceae, guanidine alkaloid, Trypanosoma cruzi