In silico design of enzyme α-amylase and α-glucosidase inhibitors using molecular docking, molecular dynamic, conceptual DFT investigation and pharmacophore modelling

Abstract

Type 2 diabetes mellitus (T2DM) is characterized by elevated blood glucose levels and can lead to serious complications such as nephropathy, neuropathy, retinopathy and cardiovascular disease. The aim of this work is to identify and investigate the inhibition mechanism of natural flavonoids and phenolics acids against, the α-amylase (αA) and α-glucosidase (αG). Therefore, we used different approaches; such as conceptual DFT and pharmacophore mapping in addition to molecular mechanics, dynamics and docking simulations. Whereas, a close agreement was found out to decide that Linarin (Flavones) provides more optimized inhibition of αA and αG enzymes. Our results have shown that Linarin could be useful as preventative agent, and possibly therapeutic modality for the treatment of metabolic diseases.

Communicated by Ramaswamy H. Sarma

Keywords:

• DFT
• flavonoids
• molecular docking
• molecular dynamic
• phenolics acids
• type 2 diabetes

Acknowledgements

Authors thank the Algerian Ministry of Higher Education and Scientific Research for the support under the PRFU project (Approval No. B00L01UN130120190009).

Disclosure statement

The authors declare no conflict of interest.

Funding

This research received no external funding.