title: The natural compounds piperovatine and piperlonguminine induce autophagic cell death on Trypanosoma cruzi.
abstract: The currently available treatments for Chagas disease show limited therapeutic potential and are associated with serious side effects. Our group has been attempting to find alternative drugs isolated from natural products as a potential source of pharmacological agents against Trypanosoma cruzi. Here, we demonstrate the antitrypanosomal activity of the amides piperovatine and piperlonguminine isolated from Piper ovatum against epimastigotes and intracellular amastigotes. We also investigated the mechanisms of action of these compounds on extracellular amastigote and epimastigote forms of T. cruzi. These amides showed low toxicity to LLCMK(2) mammalian cells. By using transmission and scanning electron microscopy, we observed that the compounds caused severe alterations in T. cruzi. These alterations were mainly located in plasma membrane and mitochondria. Furthermore, the study of treated parasites labeled with Rh123, PI and MDC corroborate with our TEM data. These mitochondrial dysfunctions induced by the amides might trigger biochemical alterations that lead to cell death. Altogether, our data evidence a possible autophagic process.
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Laboratório de Inovação Tecnológica no Desenvolvimento de Fármacos e Cosméticos, Universidade Estadual de Maringá, Paraná, Brazil.
authors.forename: Phercyles
authors.initials: P
authors.lastname: Veiga-Santos
authors.forename: Vânia Cristina
authors.initials: VC
authors.lastname: Desoti
authors.forename: Nathielle
authors.initials: N
authors.lastname: Miranda
authors.forename: Tânia
authors.initials: T
authors.lastname: Ueda-Nakamura
authors.forename: Benedito Prado
authors.initials: BP
authors.lastname: Dias-Filho
authors.forename: Sueli Oliveira
authors.initials: SO
authors.lastname: Silva
authors.forename: Diogenes Aparício Garcia
authors.initials: DA
authors.lastname: Cortez
authors.forename: João Carlos Palazzo
authors.initials: JC
authors.lastname: de Mello
authors.forename: Celso Vataru
authors.initials: CV
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000633:toxicity; D001343:Autophagy; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004148:Dioxolanes / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D015388:Organelles / Q000187:drug effects / Q000648:ultrastructure; D031701:Piper / Q000737:chemistry; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000633:toxicity; D013011:Sorbic Acid / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology / Q000633:toxicity; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000648:ultrastructure; D010881:Piperidones
chemical_list: D000981:Antiprotozoal Agents; D004148:Dioxolanes; D010936:Plant Extracts; D013011:Sorbic Acid; C038333:piperovatine; C498077:piperlongumine; D010881:Piperidones