title: Ultrastructural and morphological changes in Leishmania (Viannia) braziliensis treated with synthetic chalcones.
abstract: Cutaneous leishmaniasis has an estimated incidence of 1.5 million new cases per year and the treatment options available are old, expensive, toxic, and difficult to administer. Chalcones have shown good activity against several species of Leishmania. However few studies have discussed the mechanisms of action and drug target of this group of compounds in Leishmania. The synthetic chalcones that were evaluated in the present study were previously shown to exhibit activity against Leishmania (Viannia) braziliensis. The objective of the present study was to identify ultrastructural and morphological changes in L. (V.) braziliensis after treatment with three synthetic chalcones (1-3). Promastigotes were treated with chalcones 1-3 and evaluated by transmission and scanning electron microscopy. Cellular and nuclear morphology of the parasites, changes in membrane permeability, and DNA fragmentation in agarose electrophoresis gel were also investigated after exposure to synthetic chalcones. All three synthetic chalcones (1-3) induced ultrastructural alterations in mitochondria, intense vacuolization, two nuclei with rounding of parasites, and cellular and nuclear shrinkage. Chalcones 1-3 also induced no changes in membrane permeability, and presence of nucleosome-sized DNA fragments. Synthetic chalcones 1-3 induced ultrastructural and morphological changes, suggesting that chalcones 1-3 induce apoptosis-like cell death. Further studies should be conducted to elucidate other aspects of the action of these chalcones against Leishmania spp. and their use for the treatment of cutaneous leishmaniasis.
authors.affiliation: Programa de Pós Graduação em Biociências e Fisiopatologia, Universidade Estadual de Maringá, Avenida Colombo, 5790, Jardim Universitário, CEP 87020-900, Maringá, Paraná, Brazil.
authors.forename: Tatiane F P
authors.initials: TF
authors.lastname: de Mello
authors.affiliation: Programa de Pós Graduação em Biociências e Fisiopatologia, Universidade Estadual de Maringá, Avenida Colombo, 5790, Jardim Universitário, CEP 87020-900, Maringá, Paraná, Brazil.
authors.forename: Bruna M
authors.initials: BM
authors.lastname: Cardoso
authors.affiliation: Faculdade de Química, Universidade Federal do Pará, Rua Augusto Corrêa, 01, Guamá, CEP 66075-110, Belém, Pará, Brazil.
authors.forename: Heriberto R
authors.initials: HR
authors.lastname: Bitencourt
authors.affiliation: Departamento de Biologia Celular, Universidade Federal do Paraná, Avenida Coronel Francisco H. dos Santos, s/n, Jardim das Américas, CEP 81531-970, Curitiba, Paraná, Brazil.
authors.forename: Lucélia
authors.initials: L
authors.lastname: Donatti
authors.affiliation: Departamento de Análises Clínicas e Biomedicina, Universidade Estadual de Maringá, Avenida Colombo, 5790, Jardim Universitário, CEP 87020-900, Maringá, Paraná, Brazil.
authors.forename: Sandra M A
authors.initials: SM
authors.lastname: Aristides
authors.affiliation: Departamento de Análises Clínicas e Biomedicina, Universidade Estadual de Maringá, Avenida Colombo, 5790, Jardim Universitário, CEP 87020-900, Maringá, Paraná, Brazil.
authors.forename: Maria V C
authors.initials: MV
authors.lastname: Lonardoni
authors.affiliation: Departamento de Análises Clínicas e Biomedicina, Universidade Estadual de Maringá, Avenida Colombo, 5790, Jardim Universitário, CEP 87020-900, Maringá, Paraná, Brazil. Electronic address: tgvsilveira@uem.br.
authors.forename: Thais G V
authors.initials: TG
authors.lastname: Silveira
mesh_terms: D000818:Animals; D017209:Apoptosis; D002463:Cell Membrane Permeability / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects; D047188:Chalcones / Q000138:chemical synthesis / Q000494:pharmacology*; D006224:Cricetinae; D053938:DNA Fragmentation / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D007892:Leishmania braziliensis / Q000187:drug effects* / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects; D014617:Vacuoles / Q000187:drug effects
chemical_list: D047188:Chalcones
keywords: Apoptosis; Cell death; Chalcones; Leishmania braziliensis; Promastigotes; Ultrastructure