title: Trypanocidal structure-activity relationship for cis- and trans-methylpluviatolide.
abstract: The trypanocidal activity of racemic mixtures of cis- and trans-methylpluviatolides was evaluated in vitro against trypomastigote forms of two strains of Trypanosoma cruzi, and in the enzymatic assay of T. cruzi gGAPDH. The cytotoxicity of the compounds was assessed by the MTT method using LLC-MK2 cells. The effect of the compounds on peroxide and NO production were also investigated. The mixture of the trans stereoisomers displayed trypanocidal activity (IC50 approximately 89.3 microM). Therefore, it was separated by chiral HPLC, furnishing the (+) and (-)-enantiomers. Only the (-)-enantiomer was active against the parasite (IC50 approximately 18.7 microM). Despite being inactive, the (+)-enantiomer acted as an antagonistic competitor. Trans-methylpluviatolide displayed low toxicity for LLC-MK2 cells, with an IC50 of 6.53 mM. Furthermore, methylpluviatolide neither inhibited gGAPDH activity nor hindered peroxide and NO production at the evaluated concentrations.
authors.affiliation: Núcleo de Ciências Exatas e Tecnológicas, Universidade de Franca, Avenida Dr. Armando Salles de Oliveira, 2001, 14404-600 Franca, SP, Brazil.
authors.forename: R
authors.initials: R
authors.lastname: da Silva
authors.forename: J
authors.initials: J
authors.lastname: Saraiva
authors.forename: S
authors.initials: S
authors.lastname: de Albuquerque
authors.forename: C
authors.initials: C
authors.lastname: Curti
authors.forename: P M
authors.initials: PM
authors.lastname: Donate
authors.forename: T N C
authors.initials: TN
authors.lastname: Bianco
authors.forename: J K
authors.initials: JK
authors.lastname: Bastos
authors.forename: M L A
authors.initials: ML
authors.lastname: Silva
mesh_terms: D000818:Animals; D002460:Cell Line; D007783:Lactones / Q000737:chemistry* / Q000494:pharmacology*; D017705:Lignans / Q000737:chemistry* / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D009569:Nitric Oxide / Q000096:biosynthesis; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000737:chemistry* / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D007783:Lactones; D017705:Lignans; D014344:Trypanocidal Agents; C508932:methylpluviatolide; D009569:Nitric Oxide