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Leishmaniasis are diseases caused by parasites belonging to Leishmania genus. The treatment with pentavalent antimonials presents high toxicity. Second 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 anti-leishmanial activity of unusual dimeric flavonoids purified from Arrabidaea brachypoda1. All procedures described here had prior approval from the local animal ethics committee (approval number 018/2015) Three compounds were tested against Leishmania sp. The in vivo infection, genetically susceptible BALB/c mice were infected in the ear dermis with L. amazonensis and treated by oral (25 and 50 mg/kg) or topical (1%) routes with compound 2 starting from the second week of infection Compound 2 was the most active against promastigotes. The counting of in vitro infected macrophages showed compound 2 was also the most active against intracellular amastigotes of L. amazonensis without toxicity to the host cell. Drug combinations showed simply an additive effect suggesting the absence of interaction between amphotericin B and compound 2. Amastigotes treated with compound 2 showed alterations in the Golgi and accumulation of vesicles inside the flagellar pocket. Compound 2-treated amastigotes presented high accumulation of cytoplasmic vesicles and myelin-like figure. 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 useful for structure-active studies against Leishmania.
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