title: Benzaldehyde thiosemicarbazone derived from limonene complexed with copper induced mitochondrial dysfunction in Leishmania amazonensis.
abstract: BACKGROUND
  Leishmaniasis is a major health problem that affects more than 12 million people. Treatment presents several problems, including high toxicity and many adverse effects, leading to the discontinuation of treatment and emergence of resistant strains.
  
  
  RESULTS
  We evaluated the in vitro antileishmanial activity of benzaldehyde thiosemicarbazone derived from limonene complexed with copper, termed BenzCo, against Leishmania amazonensis. BenzCo inhibited the growth of the promastigote and axenic amastigote forms, with IC(50) concentrations of 3.8 and 9.5 µM, respectively, with 72 h of incubation. Intracellular amastigotes were inhibited by the compound, with an IC(50) of 10.7 µM. BenzCo altered the shape, size, and ultrastructure of the parasites. Mitochondrial membrane depolarization was observed in protozoa treated with BenzCo but caused no alterations in the plasma membrane. Additionally, BenzCo induced lipoperoxidation and the production of mitochondrial superoxide anion radicals in promastigotes and axenic amastigotes of Leishmania amazonensis.
  
  
  CONCLUSIONS
  Our studies indicated that the antileishmania activity of BenzCo might be associated with mitochondrial dysfunction and oxidative damage, leading to parasite death.
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Paraná, Brazil.
authors.forename: Elizandra Aparecida
authors.initials: EA
authors.lastname: Britta
authors.forename: Ana Paula Barbosa
authors.initials: AP
authors.lastname: Silva
authors.forename: Tânia
authors.initials: T
authors.lastname: Ueda-Nakamura
authors.forename: Benedito Prado
authors.initials: BP
authors.lastname: Dias-Filho
authors.forename: Cleuza Conceição
authors.initials: CC
authors.lastname: Silva
authors.forename: Rosana Lázara
authors.initials: RL
authors.lastname: Sernaglia
authors.forename: Celso Vataru
authors.initials: CV
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001547:Benzaldehydes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003300:Copper / Q000378:metabolism*; D006801:Humans; D007891:Leishmania / Q000378:metabolism*; D007896:Leishmaniasis / Q000188:drug therapy* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000469:parasitology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D013882:Thiosemicarbazones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000981:Antiprotozoal Agents; D001547:Benzaldehydes; D013882:Thiosemicarbazones; D013481:Superoxides; D003300:Copper; C032175:benzaldehyde