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

Bioorg Chem. 2021 Nov:116:105400. doi: 10.1016/j.bioorg.2021.105400. Epub 2021 Oct 2.

Abstract

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.

Keywords: Absolute configuration; Clerodane; Cystathionine γ-lyase; Diterpenoid glucosides; Tinospora sinensis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cystathionine gamma-Lyase / antagonists & inhibitors*
  • Cystathionine gamma-Lyase / metabolism
  • Density Functional Theory
  • Diterpenes / chemistry
  • Diterpenes / isolation & purification
  • Diterpenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / isolation & purification
  • Enzyme Inhibitors / pharmacology*
  • Glucosides / chemistry
  • Glucosides / isolation & purification
  • Glucosides / pharmacology*
  • Humans
  • Molecular Structure
  • Structure-Activity Relationship
  • Tinospora / chemistry*

Substances

  • Diterpenes
  • Enzyme Inhibitors
  • Glucosides
  • Cystathionine gamma-Lyase