title: Alchornedine, a new anti-trypanosomal guanidine alkaloid from Alchornea glandulosa.
abstract: Bioactivity-guided fractionation of the MeOH extract from the leaves of Alchornea glandulosa afforded a new guanidine alkaloid named alchornedine, as well as two other inactive derivatives (pteroginine and pteroginidine). The structure of alchornedine, which shows a very rare ring system, was elucidated based on NMR, IR, and MS spectral analyses. This compound displayed antiprotozoal activity against Trypanosoma cruzi (Y strain). By using the MTT assay, the trypomastigotes showed an IC50 value of 93 µg/mL (443 µM), a similar effectiveness to the standard drug benznidazole. Alchornedine also showed activity against the intracellular amastigotes, with an IC50 value of 27 µg/mL (129 µM). Using benznidazole as a 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 50 µg/mL (237 µM), but this compound demonstrated a selective elimination of parasites inside macrophages without affecting the morphology of the 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 trypanosomiasis.
authors.affiliation: Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Kaidu H
authors.initials: KH
authors.lastname: Barrosa
authors.affiliation: Centro de Parasitologia e Micologia, Instituto Adolfo Lutz, São Paulo, SP, Brazil.
authors.forename: Erika G
authors.initials: EG
authors.lastname: Pinto
authors.affiliation: Centro de Parasitologia e Micologia, Instituto Adolfo Lutz, São Paulo, SP, Brazil.
authors.forename: Andre G
authors.initials: AG
authors.lastname: Tempone
authors.affiliation: Departamento de Botânica, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Euder Glendes A
authors.initials: EG
authors.lastname: Martins
authors.affiliation: Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: João Henrique G
authors.initials: JH
authors.lastname: Lago
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D019665:Euphorbiaceae / Q000737:chemistry*; D006146:Guanidines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D014344:Trypanocidal Agents / Q000737:chemistry / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D000470:Alkaloids; D006146:Guanidines; D014344:Trypanocidal Agents; C000598855:alchornedine