Cytotoxic macrocyclic diterpenoids from Jatropha multifida

Bioorg Chem. 2018 Oct:80:511-518. doi: 10.1016/j.bioorg.2018.06.025. Epub 2018 Jun 20.

Abstract

Nine new macrocyclic diterpenoids (1-9), jatromultones A-I, along with eight known analogues (10-17) were isolated from the trunks of Jatropha multifida. The structures of the new compounds, including their absolute configurations, were elucidated by combination of spectroscopic analysis, single crystal X-ray diffraction, Rh2(OCOCF3)4-induced CD method, and chemical correlations. All compounds were screened for the cytotoxicity against five cancer cell lines, including one drug-resistant cell line, and seven compounds exhibited significant activity with IC50 values less than 10 μM. Compound 4 with IC50 values ranging from 2.69 to 6.44 μM toward all cell lines was selected for further mechanistic study, which showed that 4 could arrest cell cycle at G2/M phase and induce apoptosis. The brief structure-activity relationships (SARs) of these macrocyclic diterpenoids were also discussed.

Keywords: Absolute configuration; Cytotoxicity; Jatropha multifida; Macrocyclic diterpenoid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry*
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Crystallography, X-Ray
  • Diterpenes / chemistry*
  • Diterpenes / isolation & purification
  • Diterpenes / pharmacology*
  • Humans
  • Jatropha / chemistry*
  • Macrocyclic Compounds / chemistry*
  • Macrocyclic Compounds / isolation & purification
  • Macrocyclic Compounds / pharmacology*
  • Models, Molecular
  • Neoplasms / drug therapy
  • Neoplasms / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • Diterpenes
  • Macrocyclic Compounds