title: Dimeric flavonoids from Arrabidaea brachypoda and assessment of their anti-Trypanosoma cruzi activity.
abstract: 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.
authors.affiliation: Laboratório de Biodiversidade e Sustentabilidade, UNESP - Universidade Estadual Paulista, Coastal Campus, Parque Bitaru, CEP 11330-900, São Vicente, Brazil.
authors.forename: Cláudia Quintino
authors.initials: CQ
authors.lastname: da Rocha
authors.forename: Emerson Ferreira
authors.initials: EF
authors.lastname: Queiroz
authors.forename: Cássio Santana
authors.initials: CS
authors.lastname: Meira
authors.forename: Diogo Rodrigo Magalhães
authors.initials: DR
authors.lastname: Moreira
authors.forename: Milena Botelho Pereira
authors.initials: MB
authors.lastname: Soares
authors.forename: Laurence
authors.initials: L
authors.lastname: Marcourt
authors.forename: Wagner
authors.initials: W
authors.lastname: Vilegas
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Wolfender
mesh_terms: D000818:Animals; D029402:Bignoniaceae / Q000737:chemistry*; D001938:Brazil; D002522:Chlorocebus aethiops; D005419:Flavonoids / Q000097:blood / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects; D051379:Mice; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D014344:Trypanocidal Agents / Q000097:blood / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*; D014709:Vero Cells
chemical_list: D005419:Flavonoids; D014344:Trypanocidal Agents; C000590849:brachydin A; C000590850:brachydin B; C000590851:brachydin C