Antileishmanial activity of dimeric flavonoids isolated from arrabidaea brachypoda

• Autor(a) principal: Rocha, Vinícius P.C.
• Data de Publicação: 2019
• Outros Autores: Da Rocha, Cláudia Quintino, Queiroz, Emerson Ferreira, Marcourt, Laurence, Vilegas, Wagner [UNESP], Grimaldi, Gabriela B., Furrer, Pascal, Allémann, Eric, Wolfender, Jean-Luc, Soares, Milena B.P.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://dx.doi.org/10.3390/molecules24010001; http://hdl.handle.net/11449/188533
• topic: Arrabidaea brachypoda; Flavonoids; High content; Leishmania

Leishmaniasis are diseases caused by parasites belonging to Leishmania genus. The treatment with pentavalent antimonials present high toxicity. Secondary line drugs, such as amphotericin B and miltefosine also have a narrow therapeutic index. Therefore, there is an urgent need to develop new drugs to treat leishmaniasis. Here, we present the in vitro anti-leishmanial activity of unusual dimeric flavonoids purified from Arrabidaea brachypoda. Three compounds were tested against Leishmana sp. Compound 2 was the most active against promastigotes. Quantifying the in vitro infected macrophages revealed that compound 2 was also the most active against intracellular amastigotes of L. amazonensis, without displaying host cell toxicity. Drug combinations presented an additive effect, suggesting the absence of interaction between amphotericin B and compound 2. Amastigotes treated with compound 2 demonstrated alterations in the Golgi and accumulation of vesicles inside the flagellar pocket. Compound 2-treated amastigotes presented a high accumulation of cytoplasmic vesicles and a myelin-like structure. When administered in L. amazonensis-infected mice, neither the oral nor the topical treatments were effective against the parasite. Based on the high in vitro activity, dimeric flavonoids can be used as a lead structure for the development of new molecules that could be useful for structure-active studies against Leishmania.