Anti-Hyperglycemic Activities, Molecular Docking and Structure-Activity Relationships (SARs) Studies of Endiandric Acids and Kingianins from Endiandra kingiana

Diabetes has become a severe chronic disease worldwide with patients significantly increasing daily. Due to the side effects of insulin and oral hypoglycaemic agents employed in diabetes treatment, scientists are working hard to develop alternative approaches from natural plants that inhibit α-amylase and α-glucosidase. Consequently, by performing a phytochemical analysis on the bark of Endiandra kingiana, the present study isolated 11 cyclic polyketides. Analyses with one-dimensional and two-dimensional nuclear magnetic resonance (1D- and 2D-NMR), highresolution electron ionization mass spectrometry (HRESIMS), and comparison with previous literature confirmed the compounds characteristics. Subsequently, the compounds were screened for in vitro α-amylase and α-glucosidase inhibiting activities. Compounds 9 and 2 exhibited potent inhibition towards α-amylase at 0.0008903 ± 0.5 and 0.02 ± 0.3 mg mL−1 of half-maximal inhibitory concentration (IC50) values, respectively. In the α-glucosidase inhibition assay, compounds 10 and 5 demonstrated good inhibition with IC50 values of 0.11 ± 0.08 and 0.14 ± 0.05 mg mL−1, respectively. The molecular docking examination demonstrated that the compounds adhered to the active sites on the C-terminal of the human pancreatic α-amylase (Protein Data Bank Identification (PDB ID): 2QV4, resolution: 1.97 Å) and maltase-glucoamylase (MGAM) (PDB ID: 3TOP, resolution: 2.88 Å), agreeing with α-amylase and α-glucosidase enzymes inhibitory reactions.