Structure-guided identification of novel natural antidiabetic inhibitors: Targeting glucoamylase from saccharomycopsis fibuligera

Diabetes mellitus, a major metabolic disorder, affected approximately 537 million individuals worldwide in 2021, according to the International Diabetes Federation. The disease is associated with severe complications that impair various organs and significantly reduce patients' quality of life. Current pharmacological treatments for diabetes are often associated with adverse effects, including abdominal discomfort, bloating, and diarrhea. In previous studies, 52 medicinal plants from 22 plant families, including Apiaceae, Asteraceae, Fabaceae, and Lamiaceae, were identified as potential treatments for diabetes and other diseases. In the present study, we aimed to investigate the phytochemical composition of these plants, resulting in a collection of approximately 933 unique compounds after removing duplicates. Rigorous filtering based on Lipinski's Rule of Five yielded 844 compounds that met key drug-likeness criteria. To assess their therapeutic potential, molecular docking studies were performed to analyze the binding modes of these compounds with the Glucoamylase receptor, focusing on key interactions with the receptor’s active site. Acarbose, a well-established alpha-glucosidase inhibitor, was used as a reference drug to validate the docking protocol and benchmark the results. Subsequently, molecular dynamics simulations were conducted for the top four selected compounds and Acarbose to evaluate the stability and persistence of the receptor-ligand interactions over time. This in silico study offers valuable insights into the therapeutic potential of plant-derived compounds and supports the development of optimized glucoamylase inhibitors for diabetes management.