Antileishmanial Activity of Dimeric Flavonoids Isolated from <i>Arrabidaea brachypoda</i>
Vinícius P. C. Rocha,
Cláudia Quintino da Rocha,
Emerson Ferreira Queiroz,
Laurence Marcourt,
Wagner Vilegas,
Gabriela B. Grimaldi,
Pascal Furrer,
Éric Allémann,
Jean-Luc Wolfender,
Milena B. P. Soares
Affiliations
Vinícius P. C. Rocha
Laboratório de Engenharia Tecidual e Imunofarmacologia, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (Fiocruz), Avenida Waldemar Falcão, 121, Candeal–Salvador-BA 40296-710, Brazil
Cláudia Quintino da Rocha
Departamento de Química, Universidade Federal do Maranhão, São Luiz 65080-805, MA, Brazil
Emerson Ferreira Queiroz
School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, CMU, 1, Rue Michel Servet, 1211 Geneva, Switzerland
Laurence Marcourt
School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, CMU, 1, Rue Michel Servet, 1211 Geneva, Switzerland
Wagner Vilegas
UNESP-Campus Experimental do Litoral Paulista, Praça Infante Dom Henrique s/n°, Parque Bitaru, São Vicente–SP 11330-900, Brazil
Gabriela B. Grimaldi
Laboratório de Engenharia Tecidual e Imunofarmacologia, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (Fiocruz), Avenida Waldemar Falcão, 121, Candeal–Salvador-BA 40296-710, Brazil
Pascal Furrer
School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, CMU, 1, Rue Michel Servet, 1211 Geneva, Switzerland
Éric Allémann
School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, CMU, 1, Rue Michel Servet, 1211 Geneva, Switzerland
Jean-Luc Wolfender
School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, CMU, 1, Rue Michel Servet, 1211 Geneva, Switzerland
Milena B. P. Soares
Laboratório de Engenharia Tecidual e Imunofarmacologia, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (Fiocruz), Avenida Waldemar Falcão, 121, Candeal–Salvador-BA 40296-710, Brazil
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.
