obtainment-macrophages-from-human-monocytes-to-assess-leishmania

Obtainment of Macrophages from Human Monocytes to Assess <em>Leishmania braziliensis</em> Infection Rate and Innate Host Immune Response

Macrophages are multifunctional cells essential to the immune system function, and the primary host cell in Leishmania braziliensis (Lb) infection. These ...

Oswaldo Cruz Foundation, Gonçalo Moniz Institute

Leishmaniasis are diseases caused by parasites belonging to  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 . Three compounds were tested against  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 , 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 -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 .

Gabriela Grimaldi

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