Immunomodulatory and Antileishmanial Activity of Phenylpropanoid Dimers Isolated from Nectandra leucantha

Autor(es):Mostrar menos -

da Costa-Silva, Thais Alves ^[1] ; Grecco, Simone S. ^[2] ; de Sousa, Fernanda S. ^[3] ; Lago, Joao Henrique G. ^[3] ; Martins, Euder G. A. ^[4] ; Terrazas, Cesar A. ^{[5, 6]} ; Varikuti, Sanjay ^{[5, 6]} ; Owens, Katherine L. ^[7] ; Beverley, Stephen M. ^[7] ; Satoskar, Abhay R. ^{[5, 6]} ; Tempone, Andre G. ^[1]

Afiliação do(s) autor(es)

^[1] Adolfo Lutz Inst, Ctr Parasitol & Mycol, Sao Paulo - Brazil

^[2] Fed Univ ABC, Ctr Nat Sci & Humanities, Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Inst Environm Chem & Pharmaceut Sci, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Dept Bot, Inst Biosci, Sao Paulo - Brazil

^[5] Ohio State Univ, Dept Microbiol, Columbus, OH 43210 - USA

^[6] Ohio State Univ, Dept Pathol, Columbus, OH 43210 - USA

^[7] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 - USA

• Tipo de documento: Artigo Científico
• Fonte: Journal of Natural Products; v. 78, n. 4, p. 653-657, APR 2015.
• Citações Web of Science: 23

Resumo

Three phenylpropanoid dimers (1-3) including two new metabolites were isolated from the extract of the twigs of Nectandra leucantha using antileishmanial bioassay-guided fractionation. The in vitro antiparasitic activity of the isolated compounds against Leishmania donovani parasites and mammalian cytotoxicity and immunomodulatory effects were evaluated. Compounds 1-3 were effective against the intracellular amastigotes within macrophages, with IC50 values of 26.7, 17.8, and 101.9 mu M, respectively. The mammalian cytotoxicity, given by the 50% cytotoxic concentration (CC50), was evaluated against peritoneal macrophages. Compounds 1 and 3 were not toxic up to 290 mu M, whereas compound 2 demonstrated a CC50 value of 111.2 mu M. Compounds 1-3 also suppressed production of disease exacerbatory cytokines IL-6 and IL-10 but had minimal effect on nitric oxide production in L. donovani-infected macrophages, indicating that antileishmanial activity of these compounds is mediated via an NO-independent mechanism. Therefore, these new natural products could represent promising scaffolds for drug design studies for leishmaniasis. (AU)

• Processo FAPESP: 13/50318-7 - Natural product-based drug design: novel compounds against Leishmania (L.) infantum
• Beneficiário: André Gustavo Tempone Cardoso
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/18756-1 - Avaliação de novas alternativas terapêuticas com fármacos sintéticos em modelos in vitro e experimentais de Leishmania (L.) infantum chagasi
• Beneficiário: André Gustavo Tempone Cardoso
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/07275-5 - Estudo da resposta imune celular in vitro frente a ação de fármacos anti-Leishmania (L.) infantum
• Beneficiário: Thaís Alves da Costa Silva
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado