title: 1,3,4-Thiadiazole derivatives of R-(+)-limonene benzaldehyde-thiosemicarbazones cause death in Trypanosoma cruzi through oxidative stress.
abstract: This work evaluated the in vitro and in vivo activity of TDZ 2 on Trypanosoma cruzi amastigotes and determined the possible mechanism of action of this compound on T. cruzi death. TDZ 2 inhibited T. cruzi proliferation in vitro and had low haemolytic potential. It also induced morphological and ultrastructural alterations. We observed a reduction of cell volume, the depolarization of the mitochondrial membrane, an increase in ROS production, lipoperoxidation of the cell membrane, lipid bodies formation and production of nitric oxide, a decrease in reduced thiols levels and, presence of autophagic vacuoles. The in vivo study found a reduction of parasitemia in animals treated with TDZ 2 alone or combined with benznidazole. Altogether, the alterations induced by TDZ 2 point to an oxidative stress condition that lead to T. cruzi cell death.
authors.affiliation: Programa de Pós-graduação em Ciências Biológicas, Universidade Estadual de Maringá, Av. Colombo 5790, CEP 87020-900, Maringá, Paraná, Brazil.
authors.forename: Solange C
authors.initials: SC
authors.lastname: Martins
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Av. Colombo 5790, CEP 87020-900, Maringá, Paraná, Brazil.
authors.forename: Danielle
authors.initials: D
authors.lastname: Lazarin-Bidóia
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Av. Colombo 5790, CEP 87020-900, Maringá, Paraná, Brazil.
authors.forename: Vânia C
authors.initials: VC
authors.lastname: Desoti
authors.affiliation: Departamento de Química, Universidade Estadual de Maringá, Av. Colombo 5790, CEP 87020-900, Maringá, Paraná, Brazil.
authors.forename: Hugo
authors.initials: H
authors.lastname: Falzirolli
authors.affiliation: Departamento de Química, Universidade Estadual de Maringá, Av. Colombo 5790, CEP 87020-900, Maringá, Paraná, Brazil.
authors.forename: Cleuza C
authors.initials: CC
authors.lastname: da Silva
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Av. Colombo 5790, CEP 87020-900, Maringá, Paraná, Brazil.
authors.forename: Tania
authors.initials: T
authors.lastname: Ueda-Nakamura
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Av. Colombo 5790, CEP 87020-900, Maringá, Paraná, Brazil.
authors.forename: Sueli de O
authors.initials: SO
authors.lastname: Silva
authors.affiliation: Programa de Pós-graduação em Ciências Biológicas, Universidade Estadual de Maringá, Av. Colombo 5790, CEP 87020-900, Maringá, Paraná, Brazil; Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Av. Colombo 5790, CEP 87020-900, Maringá, Paraná, Brazil. Electronic address: cvnakamura@uem.br.
authors.forename: Celso V
authors.initials: CV
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology*; D001547:Benzaldehydes / Q000737:chemistry / Q000494:pharmacology*; D014355:Chagas Disease / Q000188:drug therapy / Q000469:parasitology; D053138:Cyclohexenes / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D000077222:Limonene; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D018384:Oxidative Stress; D059208:Parasite Load; D018512:Parasitemia / Q000188:drug therapy / Q000469:parasitology; D013729:Terpenes / Q000737:chemistry / Q000494:pharmacology*; D013830:Thiadiazoles / Q000737:chemistry / Q000494:pharmacology*; D013882:Thiosemicarbazones / Q000737:chemistry / Q000494:pharmacology*; D016896:Treatment Outcome; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology / Q000648:ultrastructure
chemical_list: D000981:Antiprotozoal Agents; D001547:Benzaldehydes; D053138:Cyclohexenes; D013729:Terpenes; D013830:Thiadiazoles; D013882:Thiosemicarbazones; C058949:1,3,4-thiadiazole; D000077222:Limonene; C032175:benzaldehyde
keywords: Cell death; Chagas' disease; Mitochondrial dysfunction; Oxidative stress; Thiadiazole