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1.
Parasitol Res ; 98(3): 218-26, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16333665

RESUMO

The study of purified alkaline phosphatase and crude extract antigen immunogenicity from Echinococcus multilocularis was carried out on BALB/c mice. The animals were immunized, then infected with E. multilocularis metacestode. The immune response against purified alkaline phosphatase was studied. Flow cytometry analysis of the CD4+ and CD8+ lymphocyte populations showed a predominance of CD4+ populations in infected immunized mice. The specific humoral response to purified alkaline phosphatase was analyzed by enzyme-linked immunosorbent assay method. We noted a stimulation of an immunoglobulin IgG response. The isotypic profile showed a prevalence of IgG1 and IgG3 in immunized infected mice compared to IgG2a and IgG2b. In addition, analysis of the profiles of the in vitro secreted cytokines, after stimulation of the splenocytes from immunized mice, was performed. The cytokine profile was a mix of Th1/Th2 types in the infected and uninfected immunized mice. The results of this study suggest a humoral mixed Th1/Th2 response, with a high predominance of Th2 response. A similar study was conducted in mice immunized with crude total antigen. The comparison of the immune response showed an important immune response in mice immunized with purified alkaline phosphatase compared to mice immunized with the crude total antigen.


Assuntos
Fosfatase Alcalina/imunologia , Equinococose/imunologia , Echinococcus multilocularis/enzimologia , Echinococcus multilocularis/imunologia , Fosfatase Alcalina/metabolismo , Animais , Anticorpos Anti-Helmínticos/sangue , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Feminino , Regulação da Expressão Gênica/fisiologia , Imunoglobulina G/sangue , Imunoglobulina G/classificação , Camundongos , Camundongos Endogâmicos BALB C , Baço/citologia
2.
Bioorg Med Chem ; 11(16): 3407-12, 2003 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-12878135

RESUMO

Boc-aminoethylindoloquinone 8, a key intermediate for the building of pentacyclic quinoneimines, analogues of kuanoniamine A, was synthesized by alkylation of 4,7-dimethoxyindole 3 with 1,2-dibromoethane followed by transformation into azide, reduction of the latter with trimethylphosphine in the presence of 2-(tert-butoxycarbonyloximino)-2-phenylacetonitrile and oxydative demethylation of the Boc-amine 6 with silver(II) oxide. Quinone 8 was then treated in situ with the thiazole o-quinodimethane 10 to afford a regioisomeric mixture of the tetracyclic quinones 11. Treatment of the mixture with trifluoroacetic acid and molecular sieves 4-A provided the corresponding quinoneimines 12. Separation of the regioisomers was performed by preparative thin-layer chromatography on silica gel. The structural assignment was made by 2D 1H-13C HMBC correlations performed on the less polar regioisomer 12b. In vitro anti-leishmanial assays showed that the tested compounds possess a good potency towards two Leishmania sp. as well as against a virulent strain of Toxoplasma gondii and without any cytotoxicity against THP-1 cells.


Assuntos
Alcaloides/síntese química , Alcaloides/farmacologia , Antiprotozoários/síntese química , Antiprotozoários/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis/química , Compostos Heterocíclicos de 4 ou mais Anéis/síntese química , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Alcaloides/química , Alcaloides/toxicidade , Animais , Antiprotozoários/química , Antiprotozoários/toxicidade , Linhagem Celular , Humanos , Concentração Inibidora 50 , Leishmania/efeitos dos fármacos , Estrutura Molecular , Toxoplasma/efeitos dos fármacos
3.
Bioorg Med Chem Lett ; 12(6): 977-9, 2002 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-11959007

RESUMO

Benzimidazole-4,7-diones derivatives substituted at 1- and/or 2-position have been synthetized and tested as inhibitors of purine nucleoside phosphorylase (PNP), isolated from two strains of Toxoplasma gondii (RH and ME 49). They were identified as inhibitors of both enzymes.


Assuntos
Antiprotozoários/síntese química , Benzimidazóis/farmacologia , Purina-Núcleosídeo Fosforilase/antagonistas & inibidores , Toxoplasma/enzimologia , Animais , Antiprotozoários/farmacologia , Benzimidazóis/síntese química , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Relação Estrutura-Atividade
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