In Silico Evaluation of Anthraquinone Derivatives as Potential α-amylase and α-glucosidase Inhibitors in Diabetes Mellitus

Diabetes mellitus (DM) is a global health concern associated with impaired glucose metabolism and postprandial hyperglycaemia. Acarbose, an α-amylase and α-glucosidase inhibitor, is widely used but causes gastrointestinal side effects. This study explores anthraquinone-based compounds as potential alternatives with fewer adverse effects. Compounds with different substituents are selected to investigate the effect of structural variations on their interactions with the key carbohydrate digestive enzymes in silico, their physicochemical and cheminformatics profiles.

Fourteen anthraquinone derivatives were investigated using web tools and in silico methods. ADME properties, drug-likeness, toxicity, and bioactivity were predicted using SwissADME, ADMETlab, ProTox 3.0, and MolPredictX tools. Molecular docking was conducted using AutoDock Vina to test their binding affinities with α-amylase (PDB: 1B2Y) and α-glucosidase (PDB: 5NN8).

All compounds followed Lipinski’s Rule of Five and exhibited binding affinities similar to acarbose. AQ12 and AQ13 demonstrated the strongest interaction with α-amylase, while AQ8 and AQ14 showed potent binding to α-glucosidase. AQ14 formed the highest number of hydrophobic bonds, enhancing binding stability. Most compounds inhibited key catalytic residues, such as His 305 in α-amylase and Asp 518 in α-glucosidase. AQ9 exhibited low predicted toxicity and favourable ADME properties.

The results support existing evidence of anthraquinones as promising antidiabetic agents, where few compounds with different structural variations display strong inhibitory potential against α-amylase and α-glucosidase, with binding interactions comparable to acarbose.

This study identifies AQ7, AQ9, and AQ12 to have valuable inhibitory potential against α-amylase and α-glucosidase, supporting their role as antidiabetic drugs. They demonstrated strong binding and favourable pharmacological properties; however further optimization and enhancement is required .