Clerodane furanoditerpenoids from the stems of Tinospora sinensis

One new clerodane-type furanoditerpenoid tinosinoid A (1) and nine new nor-clerodane analogs tinosinoids B-J (2-10) have been isolated from the stems of Tinospora sinensis. The structures of the new compounds with absolute configurations have been elucidated by spectroscopic means, including MS, NMR and ECD techniques, as well as chemical correlation. Compound 1 is a rare sulfurcontaining clerodane diterpenoid incorporating a 2-mercaptoethanol unit via a thioether bond, while compounds 4/5 and 9 represent two pairs of unusual equilibrium regioisomers through an interesting intramolecular transesterification. Our bioassays established that 1 and 8 displayed moderate antiproliferative effects against two human tumor cell lines, and 9 and 10 showed significant alpha-glucosidase inhibitory activities. A kinetics study revealed that compound 10 was a noncompetitive alpha-glucosidase inhibitor, and its possible binding mode to the enzyme was further probed by molecular docking experiments.

Automated summary

One new clerodane-type furanoditerpenoid and nine new nor-clerodane analogs have been isolated from the stems of Tinospora sinensis. The structures and absolute configurations of these compounds were determined using spectroscopic techniques and chemical correlation. Some of the compounds exhibited antiproliferative and alpha-glucosidase inhibitory activities, with compound 10 being a noncompetitive inhibitor and its binding mode to the enzyme further investigated using molecular docking experiments.