RESUMEN
A number of thiazolidin-4-one and thiazinan-4-one derivatives were prepared by three component condensation in one pot reaction method. These compounds were evaluated for anti-hyperglycemic activity by in vitro and in vivo assay systems. The compounds with thiazolidin-4-one and thiazinan-4-one moieties exhibited significant anti-hyperglycemic activity. A few compounds (3a, 3b, 4a and 4b) have exhibited both anti-hyperglycemic and anti-dyslipidemic activities. Among them the thiazinan-4-one derivative 4a showed maximal (45%) improvement in oral glucose tolerance test in db/db mice at 30 mg/kg oral dose.
Asunto(s)
Hipoglucemiantes/farmacología , Hipolipemiantes/farmacología , Tiazinas/farmacología , Tiazolidinas/farmacología , Células 3T3-L1 , Animales , Glucemia/metabolismo , Diferenciación Celular/efectos de los fármacos , Línea Celular , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/prevención & control , Relación Dosis-Respuesta a Droga , Dislipidemias/prevención & control , Glucosa/metabolismo , Glucosa/farmacocinética , Hipoglucemiantes/síntesis química , Hipoglucemiantes/química , Hipolipemiantes/síntesis química , Hipolipemiantes/química , Masculino , Ratones , Modelos Químicos , Estructura Molecular , Músculo Esquelético/citología , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Rosiglitazona , Relación Estructura-Actividad , Tiazinas/síntesis química , Tiazinas/química , Tiazolidinedionas/química , Tiazolidinedionas/farmacología , Tiazolidinas/síntesis química , Tiazolidinas/química , Triglicéridos/sangreRESUMEN
The hybrid congeners 62-90 of 6- and 7-hydroxyflavones with aminopropanol have been synthesized and evaluated for their antidiabetic activity in sucrose-challenged low-dosed streptozotocin (STZ)-induced diabetic rats and db/db mice. The optical enantiomers 70a, 70b, 90a, and 90b of two congeners 70 and 90 exhibiting consistent antidiabetic and antidyslipidemic activities were also prepared, and their antidiabetic activity results indicate its association mainly with S isomers. These compounds also lower cholesterol and TG profiles while improving high-density lipoprotein cholesterol to CHOL ratio in db/db mice. The bioavailability of compound 70 and its isomer varies between 27 and 29% whereas that of the more polar compound 90a is poor as determined in rat by oral and intraperitoneal administrations.
Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Flavonas/síntesis química , Hipoglucemiantes/síntesis química , Hipolipemiantes/síntesis química , Animales , Disponibilidad Biológica , Colesterol/sangre , Cricetinae , Relación Dosis-Respuesta a Droga , Flavonas/química , Flavonas/farmacología , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Hipolipemiantes/química , Hipolipemiantes/farmacología , Insulina/sangre , Masculino , Mesocricetus , Ratones , Ratones Endogámicos C57BL , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Estereoisomerismo , Estreptozocina , Relación Estructura-Actividad , Triglicéridos/sangreRESUMEN
A series of chalcone based PPAR-α agonists were synthesized and evaluated for their antidyslipidemic activity in high fructose high fat fed dyslipidemic Syrian golden hamsters. Most of the compounds exhibited antidyslipidemic activity. The compounds 4c and 4f have been identified as most potent antidyslipidemics. A definite structure-activity relationship was observed while varying the nature as well as the position of the substituent.