Anti-hyperglycemic activities, molecular docking and structure-activity relationships (SARs) studies of endiandric acids and kingianins from Endiandra kingiana
Document Type
Article
Publication Date
9-1-2022
Abstract
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 alpha-amylase and alpha-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), high-resolution electron ionization mass spectrometry (HRESIMS), and comparison with previous literature confirmed the compounds characteristics. Subsequently, the compounds were screened for in vitro alpha-amylase and alpha-glucosidase inhibiting activities. Compounds 9 and 2 exhibited potent inhibition towards alpha-amylase at 0.0008903 +/- 0.5 and 0.02 +/- 0.3 mg mL(-1) of half-maximal inhibitory concentration (IC50) values, respectively. In the alpha-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 alpha-amylase (Protein Data Bank Identification (PDB ID): 2QV4, resolution: 1.97 angstrom) and maltase-glucoamylase (MGAM) (PDB ID: 3TOP, resolution: 2.88 angstrom), agreeing with alpha-amylase and alpha-glucosidase enzymes inhibitory reactions.
Keywords
Endiandra kingiana, Endiandric acids, Kingianins, Alpha-amylase, Alpha-glucosidase, Molecular docking
Divisions
CHEMISTRY
Funders
Universiti Sains Malaysia Research Grant RUI (Grant No: 1001.PKIMIA.8012310),CNRS-UM; Associated International Laboratory (LIA) under FM-NatProLab
Publication Title
Journal of the Brazilian Chemical Society
Volume
33
Issue
9
Publisher
SOC BRASILEIRA QUIMICA
Publisher Location
CAIXA POSTAL 26037, 05599-970 SAO PAULO, BRAZIL