Cytotoxic and apoptosis-inducing activities against human lung cancer cell lines of cassaine diterpenoids from the bark of Erythrophleum fordii

Bioorg Med Chem Lett. 2017 Jul 1;27(13):2946-2952. doi: 10.1016/j.bmcl.2017.05.006. Epub 2017 May 4.

Abstract

A phytochemical investigation into the bark of Erythrophleum fordii yielded four new compounds, two new cassaine diterpenoids (erythrofordin T and U, 1 and 2) and two new cassaine diterpenoid amines (erythroformine A and B, 6 and 7), as well as nine known compounds. We report for the first time the isolation of erythrofordin V (3) from a natural source and that of the remaining eight known diterpenoids (4-5, 8-13) from E. fordii. All structures were elucidated using spectroscopic analysis. Cytotoxic activity of the isolated compounds (1-13) was examined in vitro against three non-small cell lung cancer cell lines (A549, NCI-H1975, and NCI-H1229) using the MTT assay. Cassaine diterpene amines (6-10, 12, 13) exhibited potent cytotoxic activity against all three cell lines with IC50 values between 0.4μM and 5.9μM. Erythroformine B (7) significantly induced apoptosis in all three cancer cells in a concentration-dependent manner.

Keywords: Apoptosis; Cassaine diterpene alkaloid; Erythrophleum fordii; Non-small cell lung cancers (NSCLC).

MeSH terms

  • Abietanes
  • Alkaloids / chemistry
  • Alkaloids / isolation & purification
  • Alkaloids / pharmacology*
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Diterpenes / chemistry
  • Diterpenes / isolation & purification
  • Diterpenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Fabaceae / chemistry*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Molecular Structure
  • Plant Bark / chemistry*
  • Structure-Activity Relationship

Substances

  • Abietanes
  • Alkaloids
  • Antineoplastic Agents, Phytogenic
  • Diterpenes
  • cassaine