Synthesis and biological evaluation of matrine derivatives as anti-hepatocellular cancer agents

Bioorg Med Chem Lett. 2016 Sep 1;26(17):4267-71. doi: 10.1016/j.bmcl.2016.07.045. Epub 2016 Jul 21.

Abstract

We delineate herein the synthesis and anti-cancer effects of 15 matrine derivatives. The in vitro growth inhibitory assays showed that most of the prepared compounds exhibited improved anti-proliferative activities towards cancer cells with IC50 17-109 times lower than that of matrine. Compounds CH6 showed the most potent anti-proliferative activities in the four tested cancer cell lines. Moreover, compound CH6 could induce G1 cell cycle arrest and inhibit cell migration in human hepatocellular cancer cell lines Bel-7402 and HepG2 through up-regulation of P21, P27 and E-cadherin and down-regulation of N-cadherin.

Keywords: Anticancer activity; Cell cycle; Hepatocarcinoma; Matrine derivatives; Migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemical synthesis
  • Alkaloids / chemistry*
  • Alkaloids / toxicity
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / toxicity*
  • Cadherins / metabolism
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Down-Regulation / drug effects
  • Drug Screening Assays, Antitumor
  • G1 Phase Cell Cycle Checkpoints / drug effects*
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Matrines
  • Quinolizines / chemical synthesis
  • Quinolizines / chemistry*
  • Quinolizines / toxicity
  • Structure-Activity Relationship
  • Up-Regulation / drug effects

Substances

  • Alkaloids
  • Antineoplastic Agents
  • Cadherins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Quinolizines
  • Cyclin-Dependent Kinase Inhibitor p27
  • Matrines