Author(s):
Rocha, Cláudia Quintino da ; Queiroz, Emerson Ferreira ; Meira, Cássio Santana ; Moreira, Diogo Rodrigo Magalhães ; Soares, Milena Botelho Pereira ; Marcourt, Laurence ; Vilegas, Wagner ; Wolfender, Jean-Luc
Date: 2014
Origin: Oasisbr
Subject(s): Bignoniaceae/química; Flavonoides/isolamento & purificação; Flavonoides/farmacologia; Tripanossomicidas/isolamento & purificação; Tripanossomicidas/farmacologia; Trypanosoma cruzi/efeitos de drogas; Brasil; Cercopithecus aethiops; Flavonoides/sangue; Flavonoides/química; Macrófagos Peritoneais/efeitos de drogas; Camundongos; Estrutura Molecular; Testes de Sensibilidade Parasitária; Tripanossomicidas/sangue; Tripanossomicidas/química; Celulas vero
Description
Universidade Estadual Paulista. Laboratório de Biodiversidade e Sustentabilidade. UNESP Coastal Campus, Parque Bitaru
The nonpolar fraction of an aqueous ethanol extract of the roots of Arrabidaea brachypoda, a Brazilian medicinal plant, demonstrated significant in vitro activity against Trypanosoma cruzi, the parasite responsible for Chagas disease. Targeted isolation of the active constituents led to the isolation of three new dimeric flavonoids (1-3), and their 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. Compound 1 exhibited no activity toward T. cruzi, while flavonoids 2 and 3 exhibited selective activity against these trypomastigotes. Compounds 2 and 3 inhibited the parasite invasion process and its intracellular development in host cells with similar potencies to benznidazole. In addition, compound 2 reduced the blood parasitemia of T. cruzi-infected mice. This study has revealed that these two dimeric flavonoids represent potential anti-T. cruzi lead compounds for further drug development.
