Dipyridamole inhibits α-amylase/α-glucosidase at sub-micromolar concentrations; in-vitro, in-vivo and theoretical studies.

Affiliation

Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address: [Email]

Abstract

Dipyridamole (DP) elevates cyclic Adenosine Monophosphate (cAMP) levels in platelets, erythrocytes, and endothelial cells and also blocks adenosine reuptake. It is used to dilate blood vessels in people with peripheral arterial disease and coronary artery disease (CAD). The flexible backbone, hydrophobic nature, and several available hydrogen bond (H-bond) donors and acceptors are well suited structural features of DP for inhibition/activation of enzymes. Substrates of α-amylase (α-Amy) and α-Glucosidase (α-Glu), known as key absorbing enzymes, have functional groups (OH groups) similar to DP. Since hypoglycemia can occur in diabetes disease and there is a significant link between diabetes and cardiovascular diseases (CVD), thus this study aimed to evaluate the inhibitory properties of DP against α-Amy and α-Glu, as enzyme targets of interest under hypoglycemia condition. DP inhibited the α-Glu and α-Amy activity in a dose dependent manner with IC50 values 19.4 ± 0.3 and 30.1 ± 0.4 µM, respectively. Further, the Ki values of DP for α-Glu and α-Amy were determined as 2.9 ± 0.2 and 3.1 ± 0.4 µM in a competitive-mode and mixed-mode inhibition, respectively. Also, DP had binding energies of -7.3 and -6.5 kcal/mol, to communicate with the active site of α-Glu and α-Amy, respectively. In addition, in-vivo studies revealed that the blood glucose concentration diminished after taking of DP compared to positive control group (p < 0.01). Accordingly, the results of the current work may prompt the scientific community to investigate the possible interconnection between DP clinical (side) effects and its α-Glu and α-Amy inhibitory properties.

Keywords

Dipyridamole,Enzyme inhibition,Hydrolyzing enzymes,Hypoglycemia,