Abstract
Background: Diabetes being among the most prevalent disease is being studied widely to achieve most potent drug with lesser side-effects. Numerous targets have been explored and several drugs have been developed to combat type-2 diabetes. Worldwide scenario depicts an increase in the number of diabetics at an alarming rate. Due to this critical need in the current scenario, the focus has been shifted to natural products. Amongst which flavonoids have been extensively studied for their anti-diabetic potential.
Among various targets inhibition of DPP-4, α-glucosidase arose as an advantageous methodology for the management of type-2 diabetes. DPP-4 inhibitor helps to maintain the insulin levels in the body and α-glucosidase inhibitor aids in the control of the postprandial glycemia.
Methods: In the present study, the molecular modeling of 155 flavonoids has been performed using GLIDE against Dipeptidyl Peptidase-4 (DPP-4) (PDB ID:2ONC) and α-glucosidase (PDB ID: 2QMJ) so as to achieve lead compounds that can be further used to develop a new drug.
Results: Rutin and Theaflavin-3,3'-di-O-gallate were observed to possess the best docking score for α-glucosidase and DPP-4 respectively.
Conclusions: The top scoring flavonoids show promising results, but further studies are required to be carried out including the pharmacophore mapping, SAR and QSAR studies. The results illustrated that the hydrogen bonding plays a crucial role in the binding and positioning of the molecules into the active site. Further, the rescoring of the docking values mentioned as MMGB/SA also reconfirmed that these compounds show favorable results.
Keywords: Type-2 diabetes, flavonoids, docking, α-glucosidase, DPP-4, binding energy.
Graphical Abstract
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