Activity of neolignans isolated from Piper regnellii (MIQ.) C. DC. var. pallescens (C. DC.) YUNCK against Trypanosoma cruzi.
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.
Luize
Patrícia Shima
PS
Mestranda do Programa de Pós-graduação em Ciências Farmacêuticas, Paraná, Brazil.
Ueda-Nakamura
Tânia
T
Dias Filho
Benedito Prado
BP
Cortez
Diógenes Aparício Garcia
DA
Nakamura
Celso Vataru
CV
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
D017705:Lignans; D010936:Plant Extracts; D014344:Trypanocidal Agents