Bioactivity-guided isolation of laevicarpin, an antitrypanosomal and anticryptococcal lactam from Piper laevicarpu (Piperaceae)

Autor(es)

Maciel, Dayany da Silva A. ^[1] ; Freitas, Viviane P. ^[1] ; Alves Conserva, Geanne A. ^[1] ; Alexandre, Tatiana R. ^[2] ; Purisco, Sonia U. ^[2] ; Tempone, Andre G. ^[2] ; Melhem, Marcia Souza C. ^[2] ; Kato, Massuo J. ^[3] ; Guimaraes, Elsie F. ^[4] ; Lago, Joao Henrique G. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, BR-09972270 Sao Paulo, SP - Brazil

^[2] Adolfo Lutz Inst, Ctr Parasitol & Micol, BR-01246000 Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Inst Quim, BR-05508000 Sao Paulo, SP - Brazil

^[4] Inst Pesquisas Jardim Bot Rio de Janeiro, BR-22460030 Rio De Janeiro, RJ - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Fitoterapia; v. 111, p. 24-28, JUN 2016.
• Citações Web of Science: 7

Resumo

Crude CH2Cl2 extract from leaves of Piper laevicarpu (Piperaceae) displayed antitrypanosomal activity against trypomastigote forms of Trypanosoma cruzi (Y strain) and antimicrobial potential against Cryptococcus gattii (strain-type WM 178). Bioactivity-guided fractionation of crude extract afforded one new natural bioactive lactam derivative, named laevicarpin. The structure of isolated compound, which displayed a very rare ring system, was elucidated based on NMR, IR and MS spectral analysis. Using MTT assay, the trypomastigotes of T. cruzi demonstrated susceptibility to laevicarpin displaying IC50 value of 14.7 mu g/mL (49.6 mu M), about 10-fold more potent than the standard drug benznidazole. The mammalian cytotoxicity of laevicarpin was verified against murine fibroblasts (NCTC cells) and demonstrated a CC50 value of 1003 mu g/mL (337.7 mu M-SI = 7). When tested against Cryptococcus gattii, laevicarpin showed an IC50 value of 2.3 mu g/mL (7.9 mu M) and a MIC value of 7.4 mu g/mL (25 mu M). Based in the obtained results, laevicarpin could be used as a scaffold for future drug design studies against the Chagas disease and anti-cryptococosis agents. (C) 2016 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 15/11936-2 - Emprego da quimiodiversidade de espécies vegetais de áreas remanescentes da Mata Atlântica do Estado de São Paulo na seleção de protótipos biologicamente ativos
• Beneficiário: João Henrique Ghilardi Lago
• Modalidade de apoio: Auxílio à Pesquisa - Regular