RESUMEN
The synthesis and biological activity of a series of 2-[(4-methylthiopyridin-2-yl)methylsulfinyl]benzimidazoles are described. These compounds have potent inhibitory effects against the protein tyrosine phosphatase activity of CD45. Enzymatic analysis with several phosphatases revealed that compound 5a had high specificity for CD45 compared with serine/threonine phosphatases (PP1, PP2A), tyrosine phosphatases (LAR, PTP1B and PTP-S2) and dual phosphatase (VHR).
Asunto(s)
Bencimidazoles/síntesis química , Inhibidores Enzimáticos/síntesis química , Proteínas Tirosina Fosfatasas/antagonistas & inhibidores , Sulfóxidos/síntesis química , Bencimidazoles/química , Bencimidazoles/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Antígenos Comunes de Leucocito/metabolismo , Proteínas Tirosina Fosfatasas/metabolismo , Relación Estructura-Actividad , Sulfóxidos/química , Sulfóxidos/farmacologíaRESUMEN
Phosphatoquinones A and B were isolated from the cultured broth of Streptomyces sp. TA-0363 and their structures were elucidated by spectroscopic analyses. Phosphatoquinones A and B inhibited the protein tyrosine phosphatase activity prepared from human Ball-1 cells with IC50 of 28 microM and 2.9 microM, respectively.
Asunto(s)
Inhibidores Enzimáticos/farmacología , Proteínas Tirosina Fosfatasas/antagonistas & inhibidores , Quinonas/farmacología , Streptomyces/metabolismo , Línea Celular , Inhibidores Enzimáticos/aislamiento & purificación , Fermentación , Humanos , Espectroscopía de Resonancia Magnética , Estructura Molecular , Quinonas/aislamiento & purificación , Espectrometría de Masa Bombardeada por Átomos Veloces , Espectrofotometría Ultravioleta , Streptomyces/química , Streptomyces/clasificaciónRESUMEN
A new platelet aggregation inhibitor, bassiatin, was isolated from the cultured broth of Beauveria bassiana which had been isolated from a soil sample collected in Yunnan province, China. The structure of bassiatin was determined to be (3S, 6R)-4-methyl-6-(1-methylethyl)-3-phenylmethyl-1, 4-perhydrooxazine-2,5-dione by NMR analysis, X-ray crystallographic analysis and chemical synthesis. Bassiatin inhibited ADP-induced aggregation of rabbit platelets with the IC50 being 1.9 x 10(-4) M.
Asunto(s)
Hongos Mitospóricos/metabolismo , Morfolinas/farmacología , Inhibidores de Agregación Plaquetaria/farmacología , Animales , Cristalografía por Rayos X , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Microscopía Electrónica de Rastreo , Hongos Mitospóricos/ultraestructura , Estructura Molecular , Morfolinas/química , Inhibidores de Agregación Plaquetaria/química , ConejosRESUMEN
Two new platelet aggregation inhibitors, PI-200 and PI-201 were isolated from the fermentation broth of Streptomyces sp. A7498. PI-200 and PI-201 inhibited ADP-induced aggregation of rabbit platelets with an IC50 of 3.8 x 10(-4) M and 7.1 x 10(-4) M, respectively.