Planta Med 2008; 74 - P-54
DOI: 10.1055/s-2008-1075250

Trypanocidal Structure-Activity Relationshipfor Cis- and Trans-methylpluviatolide

R Silva 1, J Saraiva 2, S Albuquerque 2, C Curti 3, PM Donate 4, TNC Bianco 1, JK Bastos 2, MLA Silva 1
  • 1Núcleo de Ciências Exatas e Tecnológicas – Universidade de Franca – Avenida Dr. Armando Salles de Oliveira, 2001, 14404-600, Franca, SP, Brazil
  • 2Departamento de Análises Clínicas, Toxicológicas eBromatológicas da Faculdade de Ciências Farmacêuticas de Ribeirão Preto – Universidade de São Paulo – Avenida do Café, s/n, 14040-903 – Ribeirão Preto – SP, Brazil
  • 3Departamento de Ciências Farmacêuticas da Faculdade de Ciências Farmacêuticas de Ribeirão Preto – Universidade de São Paulo – Avenida do Café, s/n, 14040-903 – Ribeirão Preto – SP, Brazil
  • 4Departamento de Química da Faculdade de Filosofia,Ciências e Letras de Ribeirão Preto – Universidade de São Paulo – Avenida Bandeirantes, 3900, 14040-901 – Ribeirão Preto – SP, Brazil

The trypanocidal activity [1–3] of racemic mixtures of cis- and trans-methylpluviatolides (2) and (1), respectively was evaluated in vitro against Trypomastigote forms of two strains of T. 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 effects of the compounds on peroxide and NO production were also investigated. The mixture of the trans stereoisomers displayed trypanocidal activity (IC50 of 89.3 µM). Therefore, it was separated by chiral HPLC, furnishing the (+) and (−)-enantiomers. Only the (−)-enantiomer was active against the parasite (IC50 of 18.7 µM) [4]. Despite being totally inactive, the (+)-enantiomer acted as an antagonistic competitor. Trans-methylpluviatolide displayed low toxicity for LLC-MK2 cells, with IC50 of 6.53 mM. Also, methylpluviatolide neither inhibit gGAPDH activity nor hinder peroxide and NO production at the evaluated concentrations. Acknowledgements: thanks to FAPESP for support for this research (Projects' 98/14956-7, 01/12006-6, 05/01550-8 and 06/60132-4). References: [1] Bastos JK, et al. (1999) Planta Med. 65: 541–544. [2] Souza VA, et al. (2005) Biorg Med Chem. 15: 303–307. [3] Da Silva Filho AA, et al. (2004) J Pharm Pharmacol. 56: 1195–1199. [4] Silva MLAE, et al. (2003) Patente WO 03080600.