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Nitro-Heterocyclic compounds induce apoptosis-like effects in Leishmania (L) amazonensis promastigotes
Mendonça, Daiane Barros Dias; Silva, Renata Ellen Costa; Palace-Berl, Fanny; Takakura, Cleusa FH; Soares, Sandra Regina C; Braz, Lucia Maria Almeida; Tavares, Leoberto Costa; Lindoso, Jose Angelo Lauletta.
Afiliação
  • Mendonça, Daiane Barros Dias; University of São Paulo. Faculty of Medicine. Laboratory of Serum Epidemiology. São Paulo. Brazil
  • Silva, Renata Ellen Costa; University of São Paulo. Faculty of Medicine. Laboratory of Serum Epidemiology. São Paulo. Brazil
  • Palace-Berl, Fanny; University of São Paulo. Faculty of Pharmacy. Department of Biochemical-Pharmaceutical Technology. Laboratory of Planning and Development of Pharmaceuticals. São Paulo. Brazil
  • Takakura, Cleusa FH; University of São Paulo. Faculty of Medicine. Department of Pathology. São Paulo. Brazil
  • Soares, Sandra Regina C; University of São Paulo. Faculty of Medicine. Institute of Tropical Medicine. Laboratory of Protozoology. São Paulo. Brazil
  • Braz, Lucia Maria Almeida; University of São Paulo. Faculty of Medicine. Laboratory of Serum Epidemiology. São Paulo. Brazil
  • Tavares, Leoberto Costa; University of São Paulo. Faculty of Pharmacy. Department of Biochemical-Pharmaceutical Technology. Laboratory of Planning and Development of Pharmaceuticals. São Paulo. Brazil
  • Lindoso, Jose Angelo Lauletta; University of São Paulo. Faculty of Medicine. Laboratory of Serum Epidemiology. São Paulo. Brazil
J. Venom. Anim. Toxins incl. Trop. Dis. ; 25: e144418, Mar. 11, 2019. ilus, tab
Article em En | VETINDEX | ID: vti-20708
Biblioteca responsável: BR68.1
ABSTRACT

Background:

Three drugs - pentavalent antimonials, amphotericin B and pentamidine - are currently used for leishmaniasis treatment. They are administered for long periods, only parenterally, and have high cardiac, renal and hepatic toxicities. Therefore, the investigation of new compounds is required. Nitro-heterocyclic derivatives have been used as possible drug candidates to treat diseases caused by trypanosomatids.

Methods:

Leishmania (L.) amazonensis promastigotes (MHO/BR/73/M2269), maintained in the Laboratório de Soroepidemiologia - Instituto de Medicina Tropical- USP, were exposed to five nitroheterocyclic derivatives, with differences at phenyl-ring position 4 BSF-C4H9, BSF-H, BSF-NO2, BSF-CH3 and BSF-Cl, for 48 hours. After analyzing viability (MTT assay), we evaluated cellular-morphology activity of compounds by transmission electron microscopy (TEM) and measurement of apoptosis (phosphatidylserine expression) by flow cytometry.

Results:

EC50 of amphotericin B and BSF-CH3 were 0.50 (M and 0.39 (M respective. Other nitro-heterocyclic compounds presented EC50 higher than amphotericin B. All compounds showed greater AV- and PI-positive expression than amphotericin B at 100 (M, except BSF-NO2. TEM showed complete nuclear disfigurement with 100 (M of BSF-NO2, 25 and 6.25 (M of BSF-H, and 6.25 (M BSF-Cl; presence of vesicles within the flagellar pocket with 25 (M BSF-H; alteration of the kinetoplast with 25 (M BSF-C4H9, 25 (M of BSF-H, 6.25 (M BSF-CH3 and 6.25 (M of BSF-Cl.

Conclusions:

Nitro-heterocyclic compounds have shown activity against promastigotes of L. amazonensis, at lower concentrations. However, improvement of compound scaffolds are needed to assist the elucidation of the mechanism of action and to achieve greater activity.(AU)
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Texto completo: 1 Base de dados: VETINDEX Assunto principal: Fosfatidilserinas / Leishmaniose / Leishmania / Nitrocompostos Limite: Animals Idioma: En Revista: J. Venom. Anim. Toxins incl. Trop. Dis. Ano de publicação: 2019 Tipo de documento: Article
Texto completo
Adicionar na Minha BVS
Imprimir
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Buscar no Google

Texto completo: 1 Base de dados: VETINDEX Assunto principal: Fosfatidilserinas / Leishmaniose / Leishmania / Nitrocompostos Limite: Animals Idioma: En Revista: J. Venom. Anim. Toxins incl. Trop. Dis. Ano de publicação: 2019 Tipo de documento: Article