Exploring Moroccan natural products as potential antidiabetic drugs: An in silico approach using molecular docking, ADMET, density functional theory and molecular dynamics simulations

Diabetes mellitus is a serious global disease characterized by high blood glucose levels, which can lead to severe complications such as cardiovascular disease, neuropathy, and kidney failure. Current treatment options are associated with significant side effects, prompting the need for developing new, more effective medications with fewer adverse effects. Several studies have explored medicinal plants used in traditional medicine for the treatment of various diseases, particularly in the development of new antidiabetic drugs. In this context, this study investigates six Moroccan medicinal plants; a virtual screening of 104 phytochemical compounds from these plants was conducted using molecular docking to assess their potential to inhibit the activity of alpha-glucosidase a key enzyme involved in glucose regulation. Compounds that exhibited significant predicted binding affinity with the target protein were subjected to ADMET analysis to evaluate their pharmacokinetic and pharmacodynamics properties and similarity to existing drugs. Three promising compounds, 16 (Catechin) and 35 (Epigallocatechin) from Ceratonia siliqua plant, and 87 (Sacranoside A) from Marrubium vulgare plant , were identified based on their good inhibitory activity against alpha-glucosidase and favorable ADMET profiles, their electronic properties were analyzed using density functional theory, and the stability of the complexes formed between these compounds and alpha-glucosidase was further evaluated through molecular dynamics simulations and MM-GBSA calculations. This computational study highlights the strong potential of Moroccan natural products as a promising candidate for further antidiabetic agents, while emphasizing that these predictions require experimental validation including in vitro and in vivo investigations.