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Neolignan Licarin A presents effect against Leishmania (Leishmania) major associated with immunomodulation in vitro
Authors:Patrícia LN Néris  John PA Caldas  Yara KS Rodrigues  Francianne M Amorim  Jacqueline A Leite  Sandra Rodrigues-Mascarenhas  José M Barbosa-Filho  Luis C Rodrigues  Márcia R Oliveira
Institution:1. Universidade Federal da Paraíba, Centro de Ciências Exatas e da Natureza, Departamento de Biologia Molecular, Laboratório de Leishmanioses, João Pessoa, Paraíba, Brazil;2. Universidade Federal da Paraíba, Centro de Biotecnologia, Laboratório de Imunofarmacologia, João Pessoa, Paraíba, Brazil;3. Universidade Federal da Paraíba, Centro de Biotecnologia, Laboratório de Síntese, João Pessoa, Paraíba, Brazil;4. Universidade Federal da Paraíba, Departamento de Ciências Farmacêuticas, João Pessoa, Paraíba, Brazil
Abstract:Leishmaniasis’ treatment is based mostly on pentavalent antimonials or amphotericin B long-term administration, expensive drugs associated with severe side effects. Considering these aforementioned, the search for alternative effective and safe leishmaniasis treatments is a necessity. This work evaluated a neolignan, licarin A anti-leishmanial activity chemically synthesized by our study group. It was observed that licarin A effectively inhibited Leishmania (Leishmania) major promastigotes (IC50 of 9.59 ± 0.94 μg/mL) growth, by inducing in these parasites genomic DNA fragmentation in a typical death pattern by apoptosis. Additionally, the neolignan proved to be even more active against intracellular amastigotes of the parasite (EC50 of 4.71 ± 0.29 μg/mL), and significantly more effective than meglumine antimoniate (EC50 of 216.2 ± 76.7 μg/mL) used as reference drug. The antiamastigote activity is associated with an immunomodulatory activity, since treatment with licarin A of the infected macrophages induced a decrease in the interleukin (IL)-6 and IL-10 production. This study demonstrates for the first time the antileishmanial activity of licarin A and suggests that the compound may be a promising in the development of a new leishmanicidal agent.
Keywords:Leishmania (Leishmania) major  Licarin A  Cytotoxicity  Macrophage  IL-6  IL-10
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