Synthesis, Characterization, and Anticancer Activity of Novel Lipophilic Emodin Cationic Derivatives

Chem Biol Drug Des. 2015 Dec;86(6):1451-7. doi: 10.1111/cbdd.12612. Epub 2015 Aug 7.


Seventeen novel emodin derivatives were synthesized, and the structures were confirmed by IR, H NMR, MS, and elemental analysis. The cytotoxic activity of the derivatives was evaluated against A375, BGC-823, HepG2, and HELF cells by MTT assay. Compound 9a with highest potency and low toxicity was selected to further investigate its detailed molecular mechanism. The lead compound 9a induced a loss of the mitochondrial transmembrane potential (▵Ψm), an increase in reactive oxygen species (ROS), release of cytochrome c and activation of caspase-3 and caspase-9. In addition, the confocal study showed that emodin derivative 9a (containing asymmetric hydrocarbon tails) was mainly localized in mitochondria, demonstrating a key role of the mitochondria-mediated apoptosis pathway in cancer cells. Taken together, the results demonstrate that embodin derivative 9a preferentially regulates the ROS-mediated apoptosis in A375 cells through the induction of cytochrome c expression and activation of caspase-3 and caspase-9 proteins.

Keywords: apoptosis; emodin derivative; reactive oxygen species; synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cytochromes c / metabolism
  • Drug Design
  • Emodin / analogs & derivatives*
  • Emodin / chemical synthesis
  • Emodin / pharmacology
  • Enzyme Activation / drug effects
  • Hep G2 Cells
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects


  • Antineoplastic Agents
  • Reactive Oxygen Species
  • Cytochromes c
  • CASP3 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 9
  • Emodin