title: Activity of neolignans isolated from Piper regnellii (MIQ.) C. DC. var. pallescens (C. DC.) YUNCK against Trypanosoma cruzi.
abstract: The in vitro antiproliferative effects of 4 neolignans purified from the ethyl-acetate extract from leaves of Piper regnellii (MIQ.) C. DC. var. pallescens (C. DC.) YUNCK against Trypanosoma cruzi were investigated. These isolated compounds were identified through spectral analyses of UV, EI-MS, 1H-, 13C-NMR, H-H COSY, gNOE, HETCOR, and HMBC. The compounds eupomatenoid-5, eupomatenoid-6, and conocarpan showed considerable activity against epimastigote forms of T. cruzi, with 50% inhibition concentrations (IC50) of 7.0, 7.5, and 8.0 microg/ml respectively. After methylation, these compounds showed a lessened inhibitory activity to the growth of the protozoan, suggesting that loss of the hydroxyl group from their molecules reduces the activity. The compound eupomatenoid-3 showed lower activity than the hexane fraction. Eupomatenoid-5 was significantly more active than benznidazole, the antiparasitic drug of choice for treatment of Chagas' disease. The crude extract, hexane fraction, and eupomatenoid-5 caused no lysis in sheep blood at concentrations which inhibit the growth of epimastigote forms. The compound eupomatenoid-5 showed low cytotoxic effects against Vero cells. These results provide new perspectives on the development of novel drugs obtained from natural products with trypanocidal activity. However, the extracts and active compound isolated from P. regnellii var. pallescens should be further studied in animal models for in vivo efficacy.
authors.affiliation: Mestranda do Programa de Pós-graduação em Ciências Farmacêuticas, Paraná, Brazil.
authors.forename: Patrícia Shima
authors.initials: PS
authors.lastname: Luize
authors.forename: Tânia
authors.initials: T
authors.lastname: Ueda-Nakamura
authors.forename: Benedito Prado
authors.initials: BP
authors.lastname: Dias Filho
authors.forename: Diógenes Aparício Garcia
authors.initials: DA
authors.lastname: Cortez
authors.forename: Celso Vataru
authors.initials: CV
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D006461:Hemolysis / Q000187:drug effects; D017705:Lignans / Q000494:pharmacology*; D031701:Piper / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology; D012756:Sheep; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*; D014709:Vero Cells
chemical_list: D017705:Lignans; D010936:Plant Extracts; D014344:Trypanocidal Agents