Pedram Routabi - Department of Biology, Faculty of Sciences, Razi University, Kermanshah, Iran
Maryam Mehrabi - Department of Biology, Faculty of Sciences, Razi University, Kermanshah, Iran
Reza Khodarahmi - Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
Hadi Adibi - Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
Masoumeh Mehrabi - Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran

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.

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