Synthesis and in silico docking studies of curcumin-polyhydroxy derivatives as novel dual inhibitors of α-amylase and α-glucosidase

Over the past twenty years, the prevalence of diabetes as one of the most common metabolic diseases hasbecome a public health problem worldwide. Blood glucose control is an important factor in delaying theonset and progression of diabetes-related complications. Therefore, in this study, curcumin- polyhydroxyderivatives were synthesized and used as effective agents in the treatment of diabetes with inhibitoryproperties against two carbohydrate-hydrolyzing enzymes α-glucosidase (α-Glu) and α-amylase (α-Amy)which are known to be significant therapeutic targets for the reduction of postprandial hyperglycemia. Insearch of potent dual inhibitors of α-Amy and α-Glu, we have synthesized curcumin-polyhydroxy derivatives,characterized by FTIR and MS then the binding interaction details of compounds to α-Amy and α-Glu weredetermined using a molecular docking study. Molecular docking was performed using AutoDock Vina anddocking results were analyzed by PyMOL v.۲.۳.۲.۱ and LigPlot+ v.۱.۴.۲ software. Molecular dockingindicated that curcumin derivatives mainly interacted with amino acid residues located in the active site ofα-Amy and α-Glu. The binding energies obtained from the docking of α-Amy with curcumin (C۱), C۲, C۳,and C۴ derivatives were -۸.۴, -۸.۲, -۸.۵ and -۸.۷, kcal/mol, respectively. Also, C۱, C۲, C۳, and C۴ derivativesshowed binding energies of -۷.۶, -۷.۸, -۸.۰ and -۸.۰ kcal/mol in communication with the active site of α-Glu,respectively. This study indicated that curcumin-polyhydroxy derivatives could occupy the active catalyticsite of α-Amy and α-Glu, resulting in the inhibitory effect due to steric hindrance, but more preclinical andclinical studies should be carried out in the future.

کلیدواژه ها:

Curcumin-based derivatives ، Anti-diabetic ، α-Amylase ، α-Glucosidase ، Molecular docking