title: Terpenes from Copaifera demonstrated in vitro antiparasitic and synergic activity.
abstract: To discover new possible therapies for Chagas' disease, we evaluated against all Trypanosoma cruzi life stages the in vitro trypanocidal and synergistic activity of terpenes isolated from Copaifera oleoresins collected in the Amazon and investigated their possible mechanism of action. Seven acid diterpenes and one sesquiterpene were tested. Terpenes promoted changes in oxidative metabolism followed by autophagic processes in the parasite cell leading to selective death. Furthermore, they were more effective against replicative forms, in particular amastigotes. A synergistic effect occurred. Cytotoxicity to erythrocytes and nucleated cells was moderate. This is the first study showing synergic activity between two terpenes against T. cruzi. Combinations of natural compounds can show high activity and may lead to new alternative treatments in the future.
authors.affiliation: Programa de Pós-Graduação em Microbiologia, Universidade Estadual de Londrina, Rodovia Celso Garcia Cid s/n 86051-990 Londrina-PR, Brazil.
authors.forename: Erika
authors.initials: E
authors.lastname: Izumi
authors.forename: Tânia
authors.initials: T
authors.lastname: Ueda-Nakamura
authors.forename: Valdir F
authors.initials: VF
authors.lastname: Veiga
authors.forename: Angelo C
authors.initials: AC
authors.lastname: Pinto
authors.forename: Celso Vataru
authors.initials: CV
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology; D004357:Drug Synergism; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D007887:Fabaceae / Q000737:chemistry*; D008018:Life Cycle Stages / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000648:ultrastructure; D018384:Oxidative Stress / Q000187:drug effects; D021261:Parasitic Sensitivity Tests; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014344:Trypanocidal Agents / Q000737:chemistry* / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000378:metabolism
chemical_list: D004224:Diterpenes; D012717:Sesquiterpenes; D013729:Terpenes; D014344:Trypanocidal Agents