Crispenes F and G, cis-Clerodane Furanoditerpenoids from Tinospora crispa, Inhibit STAT3 Dimerization

J Nat Prod. 2018 Feb 23;81(2):236-242. doi: 10.1021/acs.jnatprod.7b00377. Epub 2018 Feb 3.

Abstract

Two new cis-clerodane-type furanoditerpenes, crispenes F and G (1 and 2), together with seven known compounds, were isolated from the stems of Tinospora crispa. Crispenes F and G (1 and 2) inhibited STAT3 dimerization in a cell-free fluorescent polarization assay and were found to have significant cytotoxicity against a STAT3-dependent MDA-MB 231 breast cancer cell line, while being inactive in a STAT3-null A4 cell line. These two compounds share structural similarities with a previously reported STAT3 inhibitor, crispene E, isolated from the same plant. Molecular docking studies suggested that the molecules inhibit STAT3 by interacting with its SH2 domain.

MeSH terms

  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Dimerization
  • Diterpenes, Clerodane / chemistry*
  • Diterpenes, Clerodane / pharmacology*
  • Humans
  • Molecular Docking Simulation
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • STAT3 Transcription Factor / antagonists & inhibitors*
  • Terpenes / chemistry*
  • Terpenes / pharmacology*
  • Tinospora / chemistry*

Substances

  • Diterpenes, Clerodane
  • Plant Extracts
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Terpenes