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

Imagem de Miniatura
Arquivos
art_BARROSA_Alchornedine_a_New_AntiTrypanosomal_Guanidine_Alkaloid_from_Alchornea_2014.PDF (143.23 KB)
Citações na Scopus
19
Tipo de produção
article
Data de publicação
2014
DOI
Scopus
Web of Science
Título da Revista
ISSN da Revista
Título do Volume
Editora
GEORG THIEME VERLAG KG
Autores
BARROSA, Kaidu H.
TEMPONE, Andre G.
MARTINS, Euder Glendes A.
LAGO, Joao Henrique G.
Citação
PLANTA MEDICA, v.80, n.15, p.1310-1314, 2014
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
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.
Palavras-chave
Alchornea glandulosa, Euphorbiaceae, guanidine alkaloids, Trypanosoma cruzi
URI
https://observatorio.fm.usp.br/handle/OPI/8847
Referências
  1. Bolzani VDS, 1995, J NAT PROD, V58, P1683, DOI 10.1021/np50125a006
  2. Calvo TR, 2007, BIOL PHARM BULL, V30, P451, DOI 10.1248/bpb.30.451
  3. Cho SY, 2006, TETRAHEDRON LETT, V47, P9029, DOI 10.1016/j.tetlet.2006.10.096
  4. Conegero LD, 2003, QUIM NOVA, V26, P825, DOI 10.1590/S0100-40422003000600008
  5. Correa DS, 2011, PARASITOL RES, V109, P231, DOI 10.1007/s00436-010-2229-8
  6. Hua HM, 2004, BIOORGAN MED CHEM, V12, P6461, DOI 10.1016/j.bmc.2004.09.026
  7. Hua HM, 2007, TETRAHEDRON, V63, P11179, DOI 10.1016/j.tet.2007.08.005
  8. Laville R, 2009, J NAT PROD, V72, P1589, DOI 10.1021/np900244g
  9. Lopes FCM, 2009, BMC COMPLEM ALTERN M, V9, DOI 10.1186/1472-6882-9-15
  10. Lopes FCM, 2005, BIOL PHARM BULL, V28, P1726, DOI 10.1248/bpb.28.1726
  11. Lopes FCM, 2011, J MED FOOD, V14, P1244, DOI 10.1089/jmf.2010.0204
  12. PATIL AD, 1995, J ORG CHEM, V60, P1182, DOI 10.1021/jo00110a021
  13. Rea A, 2013, PLOS NEGLECT TROP D, V7, DOI 10.1371/journal.pntd.0002556
  14. Reimao JQ, 2010, BIOORGAN MED CHEM, V18, P8044, DOI 10.1016/j.bmc.2010.09.015
  15. Rivera G, 2009, CURR MED CHEM, V16, P3286
  16. Schmidt TJ, 2012, CURR MED CHEM, V19, P2128
  17. Takishima S, 2009, ORG LETT, V11, P2655, DOI 10.1021/ol9006794
  18. Tempone AG, 2011, PLANTA MED, V77, P572, DOI 10.1055/s-0030-1250663
  19. Ventura-Garcia L, 2013, PLOS NEGLECT TROP D, V7, DOI 10.1371/journal.pntd.0002410

Coleções
Artigos e Materiais de Revistas Científicas - IMT