RESUMO
The glutathione S-transferase (GST) was purified from fresh blood erythrocytes using affinity column chromatography. Also, α-amylase from porcine pancreas and α-glycosidase from Saccharomyces cerevisiae were used as target enzymes. In this study, these compounds were tested on α-amylase, α-glycosidase, and GST enzymes and demonstrated effective inhibitor compounds with Ki values in the range of 8.34-40.78⯵M against GST, and 120.53-892.36â¯nM against α-glycosidase. Additionally, the phenolic molecules were tested for the inhibition of α-amylase enzyme which determined effective inhibition profile with IC50 values in the range of 175.01-626.58â¯nM. Indeed, these molecules can be elective inhibitors of GST, α-glycosidase and α-amylase enzymes as antidiabetic and antiparasitic agents.
Assuntos
Antioxidantes/farmacologia , Antiparasitários/farmacologia , Glutationa Transferase/antagonistas & inibidores , Inibidores de Glicosídeo Hidrolases/farmacologia , Hipoglicemiantes/farmacologia , alfa-Amilases/antagonistas & inibidores , alfa-Glucosidases/metabolismo , Humanos , Estrutura Molecular , Espécies Reativas de Oxigênio/metabolismoRESUMO
Three 1-aminoindanes, four anilines and BnOH or t-BuOH were reacted with chlorosulfonyl isocyanate to give sulfamoyl carbamates. Pd-C catalysed hydrogenolysis reactions of carbamates or deprotection of the Boc group of the carbamates with CF3 CO2 H afforded seven novel sulfamides. Human carbonic anhydrase (hCA) isoenzymes I and II (hCA I and hCA II) were purified from fresh human blood erythrocytes with one-step affinity chromatography on Sepharose 4B-tyrosine-sulfanilamide. The inhibitory properties of the novel sulfamides on both isoenzymes were determined using the esterase activity with 4-nitrophenyl acetate (NPA) as substrate. The tested novel sulfamides derived from 1-aminoindanes and anilines effectively inhibited hCA I and II competitively in the nanomolar range. Among these compounds, the novel sulfamide derivative 17 showed the most potent inhibitory effect against hCA I (Ki : 153.88 nM), while sulfamide derivative 26 showed the highest inhibitory potential against hCA II (Ki : 117.80 nM).