α-glucosidase Inhibitory Potential and ADME-T Profile of Senna auriculata Leaf Metabolites for Antidiabetic Activity: A Molecular Docking and Dynamics Simulation Study

A BSTRACT Background: Hyperglycemia resulting from impaired insulin production or function is the underlying cause of diabetes, with type 2 diabetes mellitus (T2DM) accounting for approximately 95% of all cases. The global prevalence of T2DM is rising exponentially, affecting over 400 million individuals. Aims and Objectives: A promising strategy for managing T2DM involves inhibiting enzymes responsible for carbohydrate digestion. Materials and Methods: In this study, the α glucosidase inhibitory potential of secondary metabolites predicted from the leaf extract of Senna auriculata was evaluated using computational approaches like molecular docking and molecular dynamics simulation. Results: The results revealed that compound A7 (6 (4 chlorophenyl) 2,5,5 triphenyl 5,8 dihydro 6H azeto[1,2 a] [1,3] thiazolo[4,5 d]pyrimidine) exhibited stronger binding affinity to α glucosidase (−9.0 kcal/mol) compared to acarbose (−7.1 kcal/mol), interacting effectively with the enzyme’s catalytic residues. Additionally, A7 demonstrated favorable pharmacokinetic properties, including high gastrointestinal absorption, acceptable ADME profile, and low predicted toxicity. Molecular dynamics simulation further confirmed the stability of the A7–α glucosidase complex, with minimal fluctuations observed over a 60 ns trajectory. Conclusion: These findings suggest that compound A7 may serve as a potential α glucosidase inhibitor with therapeutic implications for diabetes management. However, further in vitro and in vivo studies are required to validate its efficacy and safety. This study concludes that compound A7 could contribute to the management of noninsulin dependent T2DM.