title: 4-Nitrobenzaldehyde thiosemicarbazone: a new compound derived from S-(-)-limonene that induces mitochondrial alterations in epimastigotes and trypomastigotes of Trypanosoma cruzi.
abstract: Trypanosoma cruzi is the causative agent of Chagas' disease, a parasitic disease that remains a serious health concern with unsatisfactory treatment. Drugs that are currently used to treat Chagas' disease are partially effective in the acute phase but ineffective in the chronic phase of the disease. The aim of the present study was to evaluate the antitrypanosomal activity and morphological, ultrastructural and biochemical alterations induced by a new molecule, 4-nitrobenzaldehyde thiosemicarbazone (BZTS), derived from S-(-)-limonene against epimastigote, trypomastigote and intracellular amastigote forms of T. cruzi. BZTS inhibited the growth of epimastigotes (IC50 = 9·2 μ m), intracellular amastigotes (IC50 = 3·23 μ m) and inhibited the viability of trypomastigotes (EC50 = 1·43 μ m). BZTS had a CC50 of 37·45 μ m in LLCMK2 cells. BZTS induced rounding and distortion of the cell body and severely damaged parasite mitochondria, reflected by extensive swelling and disorganization in the inner mitochondrial membrane and the presence of concentric membrane structures inside the organelle. Cytoplasmic vacuolization, endoplasmic reticulum that surrounded organelles, the loss of mitochondrial membrane potential, and increased mitochondrial O2 •- production were also observed. Our results suggest that BZTS alters the ultrastructure and physiology of mitochondria, which could be closely related to parasite death.
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas,Universidade Estadual de Maringá,PR,Avenida Colombo,5790,Jd. Universitário,Maringá,Paraná 87020-900,Brazil.
authors.forename: Elizandra Aparecida
authors.initials: EA
authors.lastname: Britta
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas,Universidade Estadual de Maringá,PR,Avenida Colombo,5790,Jd. Universitário,Maringá,Paraná 87020-900,Brazil.
authors.forename: Débora Botura
authors.initials: DB
authors.lastname: Scariot
authors.affiliation: Departamento de Química,Universidade Estadual de Maringá,Maringá,PR,Avenida Colombo,5790,Jd. Universitário,Maringá,Paraná 87020-900,Brazil.
authors.forename: Hugo
authors.initials: H
authors.lastname: Falzirolli
authors.affiliation: Departamento de Química,Universidade Estadual de Maringá,Maringá,PR,Avenida Colombo,5790,Jd. Universitário,Maringá,Paraná 87020-900,Brazil.
authors.forename: Cleuza Conceição
authors.initials: CC
authors.lastname: da Silva
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas,Universidade Estadual de Maringá,PR,Avenida Colombo,5790,Jd. Universitário,Maringá,Paraná 87020-900,Brazil.
authors.forename: Tânia
authors.initials: T
authors.lastname: Ueda-Nakamura
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas,Universidade Estadual de Maringá,PR,Avenida Colombo,5790,Jd. Universitário,Maringá,Paraná 87020-900,Brazil.
authors.forename: Benedito Prado
authors.initials: BP
authors.lastname: Dias Filho
authors.affiliation: Univ. Grenoble Alpes,CERMAV-CNRS UPR 5301,F-38000 Grenoble,France.
authors.forename: Redouane
authors.initials: R
authors.lastname: Borsali
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas,Universidade Estadual de Maringá,PR,Avenida Colombo,5790,Jd. Universitário,Maringá,Paraná 87020-900,Brazil.
authors.forename: Celso Vataru
authors.initials: CV
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D001547:Benzaldehydes / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D053138:Cyclohexenes / Q000737:chemistry*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D004847:Epithelial Cells / Q000187:drug effects / Q000469:parasitology; D008018:Life Cycle Stages / Q000187:drug effects* / Q000502:physiology; D000077222:Limonene; D008253:Macaca mulatta; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D013481:Superoxides / Q000819:agonists / Q000378:metabolism; D013729:Terpenes / Q000737:chemistry*; D013882:Thiosemicarbazones / Q000737:chemistry / Q000494:pharmacology; D014344:Trypanocidal Agents / Q000737:chemistry / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D001547:Benzaldehydes; D053138:Cyclohexenes; D013729:Terpenes; D013882:Thiosemicarbazones; D014344:Trypanocidal Agents; D013481:Superoxides; D000077222:Limonene
keywords: 4-nitrobenzaldehyde thiosemicarbazone; Trypanosoma cruzi; antitrypanosomal activity; cell death; mitochondria alterations