Planta Med 2014; 80 - SL39
DOI: 10.1055/s-0034-1394527

Unusual dimeric flavonoids from Arrabidaea brachypoda with very significant in vitro and in vivo anti-Trypanosoma cruzi activity

C Quitino-da-Rocha 1, E Ferreira-Queiroz 2, C Santana-Meira 3, DR Magalhães-Moreira 3, M Botelho-Pereira-Soares 3, L Marcourt 2, W Vilegas 1, JL Wolfender 2
  • 1Laboratório de Biodiversidade e Sustentabilidade, Campus Experimental do Litoral Paulista, Universidade Estadual Paulista (UNESP), Parque Bitaru, CEP 11330 – 900, São Vicente, Brazil
  • 2School of Pharmaceutical Sciences, Phytochemistry and Bioactive Natural Products, University of Geneva, University of Lausanne, CH-1211 Geneva 4, Switzerland
  • 3Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz (Fiocruz), Candeal, CEP 40296 – 710, Salvador, Brazil

Chagas disease is a parasitic disease caused by the flagellate protozoan Trypanosoma cruzi. This disease is transmitted to humans mainly in rural endemic areas through the infected feces of triatomine insects. However, when infected people from rural regions began to migrate to cities the disease was then spread to different non-endemic areas [1]. The World Health Organization (WHO) reports that globally approximately 10 million people are infected by T. cruzi, and more than 25 million people are at risk of infection in endemic countries [2]. The aqueous ethanol extract of the roots of Arrabidaea brachypoda, a Brazilian medicinal plant, exhibited significant in vitro activity against T. cruzi, the parasite responsible for Chagas disease. Targeted isolation of the active constituents led to the isolation of three unusual dimeric flavonoids. The structures were elucidated using UV, NMR and HRMS analysis, as well as by chemical derivatization. The anti-T. cruzi activity and cytotoxicity toward mammalian cells were determined for these substances. Two compounds exhibited selective activity against the trypomastigotes and also inhibited the parasite invasion process and its intracellular development in host cells with similar potencies to benznidazole. In addition one compound reduced the blood parasitemia of T. cruzi-infected mice. This study revealed that these two dimeric flavonoids represent potential anti-T. cruzi lead compounds for further drug development.

Keywords: Arrabidaea brachypoda, dimeric flavonoids, Trypanosoma cruzi, in vitro, in vivo

References:

[1] Carabarin-Lima A, Gonzalez-Vazquez MC, Rodriguez-Morales O, Baylon-Pacheco L, Rosales-Encina JL, Reyes-Lopez PA, Arce-Fonseca M. (2013) Acta tropica, 127, 126 – 135.

[2] WHO. World Health Organization. Chagas Disease: Control and Elimination; 2010.