Diterpenoid glucosides with cystathionine γ-lyase inhibitory activity from Tinospora sinensis

Fifteen previously undescribed nor-clerodane diterpenoid glucosides tinosinesides C-Q (1-15), along with four known analogues (16-19), were isolated from the stems of Tinospora sinensis. The structures of the new compounds were elucidated by spectroscopic means, and their absolute configurations were established on the basis of time-dependent density functional theory (TD-DFT) based electronic circular dichroism (ECD) calculation and chemical methods. All the isolates were evaluated for their inhibitory effects on cystathionine γ-lyase (CSE), a natural enzyme responsible for the synthesis of H₂S. Compounds 4 and 5 represent rare examples of natural CSE inhibitors and the possible binding mode to CSE was further probed by molecular docking experiment.