ent-Labdane and ent-kaurane diterpenoids from Chelonopsis odontochila with α-glucosidase inhibitory activity

Eleven new ent-labdane diterpenoids, cheodontoins A-K (1-11), and thirteen known diterpenoids involving two ent-labdanes (12-13) and eleven ent-kauranes (14-24), were isolated from the active part of Chelonopsis odontochila (Lamiaceae) under the guidance of bioassay. The structures of cheodontoins A-K (1-11) were elucidated by extensive HRESIMS, 1D and 2D NMR, [alpha](D) and ECD experiments, X-ray diffraction and quantum calculation. Interestingly, five nor-ent-labdanes (9-13) were obtained from this genus for the first time. One ent-labdane diterpenoid (12) and four ent-kaurane diterpenoids (16, 19, 23, and 24) showed a-glucosidase inhibitory activity with IC50 values of 326.5 +/- 3.5, 599.1 +/- 13.8, 620.1 +/- 16.1, 185.0 +/- 4.2, and 190.7 +/- 11.6 mu M, respectively. Compounds 12 and 16 were a-glucosidase mixed-type inhibitors with K-i values of 334.1 and 589.2 mu M according to the enzyme kinetics using Lineweaver-Burk and Dixon plots. Docking study manifested that compounds 12 and 23 well located in the catalytic pocket of a-glucosidase by hydrophobic effects with Trp1355, Trp1369, Phe1427, Phe1559, and Phe1560 residues. This study provides new insights for the antidiabetic effects of C. odontochila with ent-labdane and ent-kaurane diterpenoids as the active constituents.