Alchornedine, a New Anti-Trypanosomal Guanidine Alkaloid from Alchornea glandulosa

Autor(es)

Barrosa, Kaidu H. ^[1] ; Pinto, Erika G. ^{[2, 3]} ; Tempone, Andre G. ^[2] ; Martins, Euder Glendes A. ^[4] ; Lago, Joao Henrique G. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, BR-09972270 Sao Paulo - Brazil

^[2] Adolfo Lutz Inst, Ctr Parasitol & Micol, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Med Trop Sao Paulo, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Dept Bot, Inst Biociencias, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Planta Medica; v. 80, n. 15, p. 1310-1314, OCT 2014.
• Citações Web of Science: 8

Resumo

Bioactivity-guided fractionation of the MeOH extract from the leaves of Alchornea glandulosa afforded a newguanidine 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 mu g/mL (443 mu M), a similar effectiveness to the standard drug benznidazole. Alchornedine also showed activity against the intracellular amastigotes, with an IC50 value of 27 mu g/mL (129 mu M). 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 mu g/mL (237 mu M), 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. (AU)

• Processo FAPESP: 11/51739-0 - Uso sustentável da biodiversidade de áreas remanescentes da Mata Atlântica do Estado de São Paulo: avaliação, isolamento e caracterização molecular de metabólitos secundários bioativos em espécies vegetais
• Beneficiário: João Henrique Ghilardi Lago
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Regular