title: Evaluation of antileishmanial activity of eupomatenoid-5, a compound isolated from leaves of Piper regnellii var. pallescens.
abstract: 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.
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Departamento de Análises Clínicas, Universidade Estadual de Maringá, Av. Colombo 5790, Paraná, Brazil.
authors.forename: Michele Cristina
authors.initials: MC
authors.lastname: Vendrametto
authors.forename: Adriana Oliveira dos
authors.initials: AO
authors.lastname: Santos
authors.forename: Celso Vataru
authors.initials: CV
authors.lastname: 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: Tânia
authors.initials: T
authors.lastname: Ueda-Nakamura
mesh_terms: 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*
chemical_list: D000981:Antiprotozoal Agents; D001572:Benzofurans; D010636:Phenols; C452811:eupomatenoid 5