Diterpenoids with diverse scaffolds from Vitex trifolia as potential topoisomerase I inhibitor

Fitoterapia. 2017 Jul:120:108-116. doi: 10.1016/j.fitote.2017.06.006. Epub 2017 Jun 8.

Abstract

Eleven new compounds, including six labdane (1-6), three halimane (7-9), and two clerodane (10-11) diterpenoids and 16 known analogues (12-27), were isolated from the leaves of Vitex trifolia. The structures of 1-11 were established by extensive 1D- and 2D-NMR and HRMS spectroscopic data. The absolute configurations of compounds 3, 7, and 10 were assigned using X-ray diffraction. Compounds 1-27 were evaluated for DNA topoisomerases I (Top1) inhibitory activity and cytotoxicity against HCT 116 cells. Compounds 8 and 11 exhibited equipotent Top1 inhibitory activity to the positive control, camptothecin (CPT), at 100μM. Compounds 8, 9, 16, and 27 showed moderate cytotoxicity at low micromolar concentrations.

Keywords: Cytotoxicity; DNA topoisomerases I; Diterpenoids; Vitex trifolia; X-ray.

MeSH terms

  • DNA Topoisomerases, Type I
  • Diterpenes
  • Diterpenes, Clerodane / chemistry*
  • Diterpenes, Clerodane / isolation & purification
  • HCT116 Cells
  • Humans
  • Molecular Structure
  • Plant Leaves / chemistry
  • Topoisomerase I Inhibitors / chemistry*
  • Topoisomerase I Inhibitors / isolation & purification
  • Vitex / chemistry*
  • X-Ray Diffraction

Substances

  • Diterpenes
  • Diterpenes, Clerodane
  • Topoisomerase I Inhibitors
  • halimane
  • labdane
  • DNA Topoisomerases, Type I
  • TOP1 protein, human