Tertiary Structure Prediction of α-Glucosidase and Inhibition Properties of N-(Phenoxydecyl) Phthalimide Derivatives

摘要

Due to increasing of population of diabetic patients, identifying factors for disease control has received much attention, α-glucosidase (EC 3.2.1.20) is an essential enzyme that helps to digestion of carbohydrates such as starch and sugar. Carbohydrates are normally converted into simple sugars, which can be absorbed through the intestine. Therefore, α-glucosidase inhibitors can be used to decrease the blood sugar level. We have studied the effect of inhibition of N-(phe-noxydecyl) phthalimide derivatives by a computer drug-design protocol involving homology modeling, docking simulation and Quantitative Structure Activity Relationship. The homology modeling of α-glucosidase showed a structure very similar to the crystal structure of oligo-1,6-glucosidase from Saccharomyces cerevisiae. Docking results showed the position of inhibitors binding site is close to active site and the carboxyl oxygen in phthalimide is an effective functional group for binding inhibitors to protein. The equation obtained by QSAR showed that, logIC_(50) decreases and so inhibition property increases when the size, polarity, geometry and number of halogen factors increase.