RESUMEN
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.
Asunto(s)
Fosfatasa Alcalina/inmunología , Equinococosis/inmunología , Echinococcus multilocularis/enzimología , Echinococcus multilocularis/inmunología , Fosfatasa Alcalina/metabolismo , Animales , Anticuerpos Antihelmínticos/sangre , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Femenino , Regulación de la Expresión Génica/fisiología , Inmunoglobulina G/sangre , Inmunoglobulina G/clasificación , Ratones , Ratones Endogámicos BALB C , Bazo/citologíaRESUMEN
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.
Asunto(s)
Alcaloides/síntesis química , Alcaloides/farmacología , Antiprotozoarios/síntesis química , Antiprotozoarios/farmacología , Compuestos Heterocíclicos de 4 o más Anillos/química , Compuestos Heterocíclicos de 4 o más Anillos/síntesis química , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Alcaloides/química , Alcaloides/toxicidad , Animales , Antiprotozoarios/química , Antiprotozoarios/toxicidad , Línea Celular , Humanos , Concentración 50 Inhibidora , Leishmania/efectos de los fármacos , Estructura Molecular , Toxoplasma/efectos de los fármacosRESUMEN
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.