RESUMEN
Gokshuradi Yog (GY) is a polyherbal ayurvedic formulation used traditionally for several decades in India for the treatment of urolithiasis. The aim of the present study was to determine the underlying mechanism of GY action in the management of calcium oxalate urolithiasis. The effect of Gokshuradi polyherbal aqueous extracts (GPAEs) was studied on various biochemical parameters involved in calcium oxalate formation by employing in vitro and in vivo methods. GPAE exhibited significant antioxidant activity against 1, 1-diphenyl-2-picrylhydrazyl free radical and inhibited lipid peroxidation in the in vitro experiments. The rat model of urolithiasis induced by 0.75% ethylene glycol (EG) and 1% ammonium chloride (AC) in water caused polyuria, weight loss, impairment of renal function, and oxidative stress and decreased antioxidant enzyme activities in untreated control groups. However, GPAE- (25, 50, and 100 mg/kg) treated groups caused diuresis accompanied by a saluretic effect and revealed significant increase in antioxidant enzyme activities along with decreased oxalate synthesizing biochemical parameters at higher doses. This study revealed the antiurolithic effect of GPAE mediated possibly through inhibiting biochemical parameters involved in calcium oxalate formation, along with its diuretic and antioxidant effects, hence supporting its use in the treatment of calcium oxalate urolithiasis.
RESUMEN
A novel series of carbazole substituted aminopyrimidines (5a-p) were synthesized and screened for their in vitro urease inhibition and antimicrobial activity. Among the compounds, 4-(2,4-dichlorophenyl)-6-(9-methyl-9H-carbazol-3-yl)-pyrimidin-2-amine (5i) was found to be the most potent showing urease inhibitory activity with an IC50 value 19.4 ± 0.43 µM. Compounds 5c, 5g, 5j and 5o showed good activity against all selected bacterial strains and compounds 5b, 5c, 5m and 5o showed good activity against selected fungal strains. All the compounds were subjected for ADME predictions by computational method.
Asunto(s)
Antibacterianos/síntesis química , Antibacterianos/farmacología , Antifúngicos/síntesis química , Antifúngicos/farmacología , Inhibidores Enzimáticos/farmacología , Pirimidinas/farmacología , Ureasa/antagonistas & inhibidores , Antibacterianos/química , Antifúngicos/química , Bacterias/efectos de los fármacos , Canavalia/enzimología , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Hongos/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Pirimidinas/síntesis química , Pirimidinas/química , Relación Estructura-Actividad , Ureasa/metabolismoRESUMEN
Claisen-Schmidt condensation of 3-formyl-9-methylcarbazole with various amides of 3-aminoacetophenone afforded N-{3-[3-(9-methyl-9H-carbazol-3-yl)-acryloyl]-phenyl}-benzamide/amide derivatives. All compounds were investigated for their in vitro xanthine oxidase (XO), tyrosinase and melanin production inhibitory activity. Most of the target compounds had more potent XO inhibitory activity than the standard drug (IC(50) = 4.3-5.6 µM). Interestingly, compound 7q bearing cyclopropyl ring was found to be the most potent inhibitor of XO (IC(50) = 4.3 µM). Molecular modelling study gave an insight into its binding modes with XO. Compounds 7a, 7d, 7e, 7g, and 7k were found to be potent inhibitors of tyrosinase (IC(50) = 14.01-17.52 µM). These results suggest the possible use of these compounds for the design and development of novel XO and tyrosinase inhibitors.