Dipyridamole inhibits Œ±-amylase/Œ±-glucosidase at sub-micromolar concentrations; in-vitro, in-vivo and theoretical studies
Authors: Sajad Moradi
Bahareh Shahmoradi
Sarwar Azizian
Reza Khodarahmi
Sajjad Esmaeili
Mohsen Shahlaei
Journal: Bioorganic Chemistry (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Dipyridamole; Enzyme inhibition; Hydrolyzing enzymes; Hypoglycemia.
Affiliations: Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address: ., Department of Pharmacognosy and Biotechnology, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran., Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran., Nano Drug Deliver Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran., Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran., Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Pharmacognosy and Biotechnology, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address: .

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 Œ±-amylase (Œ±-Amy) and Œ±-Glucosidase (Œ±-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 Œ±-Amy and Œ±-Glu, as enzyme targets of interest under hypoglycemia condition. DP inhibited the Œ±-Glu and Œ±-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 Œ±-Glu and Œ±-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 Œ±-Glu and Œ±-Amy, respectively. In addition, in-vivo studies revealed that the blood glucose concentration diminished after taking of DP compared to positive control group (p &lt; 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 Œ±-Glu and Œ±-Amy inhibitory properties. 

Retracted: No

PubPeer comments:
 **Concern** PDB ids of human **alpha-amylase (1HNY) and alpha-glucosidase (5NN8)** have been formerly crystalized but authors don t use them as input queries for docking and simulation analyses. The results are not citable because the credibility of the computational section cannot be approved. Dipyridamole has significant side effects and considering it as a potential anti-diabetic agent is not rationale. ,