Evaluation of antileishmanial activity of eupomatenoid-5, a compound isolated from leaves of Piper regnellii var. pallescens.
Infection with Leishmania spp. causes a disease with multifaceted clinical manifestations in humans. The treatment for leishmaniasis is dependent on a limited range of drugs. Here we investigated the antileishmanial activity of eupomatenoid-5, a neolignan isolated from leaves of Piper regnellii var. pallescens. We showed that eupomatenoid-5 had a dose-dependent activity during 72h of treatment, exhibiting IC(50) of 9.0microg/mL and 13.0microg/mL for promastigote and axenic amastigote forms, respectively, and IC(50) of 5.0microg/mL for intracellular amastigote forms of Leishmania amazonensis. When L. amazonensis was treated with eupomatenoid-5, it underwent considerable ultrastructural alterations, as shown by transmission electron microscopy. Among the alterations was the appearance of intense exocytic activity in the region of the flagellar pocket, myelin-like figures, and vacuoles in the cytoplasm of parasites treated with 9.0microg/mL. Cells treated with 25.0microg/mL showed a very large structure, apparently an extension of the endoplasmic reticulum. Also, mitochondrial swelling was detected at this concentration, indicating damage and significant change in this organelle. A cytotoxicity assay showed that the action of the isolated compound is more specific for protozoa and it is not toxic to macrophages. Our studies indicated that eupomatenoid-5 might be a potential new drug for the treatment of leishmaniasis, because this compound displays interesting antileishmanial activity in vitro against promastigote, axenic amastigote, and intracellular amastigote forms of L. amazonensis.
Vendrametto
Michele Cristina
MC
Programa de Pós-graduação em Ciências Farmacêuticas, Departamento de Análises Clínicas, Universidade Estadual de Maringá, Av. Colombo 5790, Paraná, Brazil.
Santos
Adriana Oliveira dos
AO
Nakamura
Celso Vataru
CV
Dias Filho
Benedito Prado
BP
Cortez
Diógenes Aparício Garcia
DA
Ueda-Nakamura
Tânia
T
D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D001572:Benzofurans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007891:Leishmania / Q000145:classification / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D007896:Leishmaniasis / Q000188:drug therapy / Q000469:parasitology; D008264:Macrophages / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D021261:Parasitic Sensitivity Tests; D010636:Phenols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D031701:Piper / Q000737:chemistry*; D018515:Plant Leaves / Q000737:chemistry*
D000981:Antiprotozoal Agents; D001572:Benzofurans; D010636:Phenols; C452811:eupomatenoid 5