Design, synthesis, and structure-activity relationship studies of novel millepachine derivatives as potent antiproliferative agents

Eur J Med Chem. 2012 Aug:54:793-803. doi: 10.1016/j.ejmech.2012.06.034. Epub 2012 Jun 23.

Abstract

In this paper, 38 millepachine derivatives have been designed, synthesized and evaluated for their in vitro and in vivo antiproliferative activity. Among these novel derivatives, 15 displayed more potent antiproliferative activity than millepachine against HepG2, K562, SK-OV-3, HCT116, HT29, and SW620 tumor cells (mean IC(50) = 0.64 vs. 2.86 μM, respectively). Furthermore, 15 could effectively inhibit tubulin polymerization in HepG2 cells, and induce the HepG2 cell cycle arrest at the G2/M phase in a concentration-dependant manner. Further studies confirmed that 15 significantly suppressed the growth of tumor volume and exerted more potent anticancer potency than millepachine and anticancer drug cisplatin in A549 lung xenograft tumor model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Benzopyrans / chemical synthesis*
  • Benzopyrans / chemistry
  • Benzopyrans / pharmacology*
  • Biological Products / chemical synthesis*
  • Biological Products / chemistry
  • Biological Products / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chalones / chemical synthesis*
  • Chalones / chemistry
  • Chalones / pharmacology*
  • Chemistry Techniques, Synthetic
  • Drug Design*
  • Humans
  • Inhibitory Concentration 50
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Benzopyrans
  • Biological Products
  • Chalones