title: Diterpenoids from Azorella compacta (Umbelliferae) active on Trypanosoma cruzi.
abstract: The anti-Trypanosoma cruzi activity of natural products isolated from Azorella compacta was evaluated, with particular emphasis on their effect against intracellular amastigotes. Five diterpenoids from A. compacta derived from mulinane and azorellane were isolated and identified. Only two products, named azorellanol (Y-2) and mulin-11,3-dien-20-oic acid (Y-5), showed trypanocidal activity against all stages of T. cruzi including intracellular amastigotes. At 10  M, these compounds displayed a strong lytic activity. It ranged from 88.4   0.6 to 99.0   1 % for all strains and stages evaluate, with an IC50 /18 h values of 20-84  M and 41-87  M, respectively. The development of intracellular amastigotes was also inhibited by nearly 60% at 25  M. The trypanocidal molecules Y-2 and Y-5 did show different degrees of cytotoxicity depending on the cell line tested, with an IC50 /24 h ranging from 33.2 to 161.2  M. We evaluated the effect of diterpenoids against intracellular T. cruzi forms by immunofluorescent identification of a specific membrane molecular marker (Ssp-4 antigen) of the T. cruzi amastigote forms. The accuracy and reproducibility of the measurements were found to be outstanding when examined by confocal microscopy.
authors.affiliation: Unidad de Parasitolog a, Departamento de Tecnolog a M dica, Universidad de Antofagasta.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Araya
authors.forename: Iván
authors.initials: I
authors.lastname: Neira
authors.forename: Solange
authors.initials: S
authors.lastname: da Silva
authors.forename: Renato A
authors.initials: RA
authors.lastname: Mortara
authors.forename: Patricio
authors.initials: P
authors.lastname: Manque
authors.forename: Esteban
authors.initials: E
authors.lastname: Cordero
authors.forename: Hernán
authors.initials: H
authors.lastname: Sagua
authors.forename: Alberto
authors.initials: A
authors.lastname: Loyola
authors.forename: Jorge
authors.initials: J
authors.lastname: Bórquez
authors.forename: Glauco
authors.initials: G
authors.lastname: Morales
authors.forename: Jorge
authors.initials: J
authors.lastname: González
mesh_terms: D000818:Animals; D019068:Bryopsida / Q000737:chemistry*; D002478:Cells, Cultured / Q000187:drug effects; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D007928:Lethal Dose 50; D018613:Microscopy, Confocal; D010936:Plant Extracts / Q000737:chemistry; D015203:Reproducibility of Results; D014344:Trypanocidal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D004224:Diterpenes; D010936:Plant Extracts; D014344:Trypanocidal Agents