Molecular dynamics simulation and pharmacokinetics studies of ombuin and quercetin against human pancreatic α-amylase

Diabetes mellitus (DM) is a group of metabolic disorders characterised by chronic hyperglycaemia. DM is currently one of the top ten causes of death in humans. Chronic hyperglycaemia in DM leads to long-term damage and failure of different organs in the body. Type 2 DM (T2D) is the most common DM form, characterised by peripheral insulin resistance, relative insulin deficiency, impaired hepatic glucose production regulation and pancreatic β cell dysfunction. The human pancreatic α-amylase (HPA) inhibitor is currently one of the most effective methods developed to inhibit hyperglycaemia in T2D patients. However, the current standard drug available, acarbose, has been associated with severe side effects following prolonged use in patients. Therefore, an alternative drug capable of effectively inhibiting HPA with minimal side effects is required. Based on our previous study, we further explored the therapeutic potential of quercetin and ombuin via molecular dynamics (MD) simulation. The Desmond Simulation Package was used to run 100-ns MD simulations to examine the steady nature and conformational stability of the ligand-HPA complexes. Post-simulation molecular mechanics-generalised born surface area (MM-GBSA) analysis of HPA's binding free energy with quercetin and ombuin was explored. The lead compounds' drug-likeness, absorption, distribution, metabolism and elimination properties were also studied using the SwissADME tool. These results indicate that quercetin and ombuin have great potential as anti-DM drugs with more favourable properties than acarbose.Communicated by Ramaswamy H. Sarma.