One-pot Synthesis and Antitumor Activity of Unsymmetrical Terphenyls

Drug Res (Stuttg). 2017 Jan;67(1):25-31. doi: 10.1055/s-0042-114776. Epub 2016 Sep 14.

Abstract

In this paper a simple and efficient method for the unsymmetrical terphenyls via sequential one-pot Suzuki coupling reactions using Pd(OAc)2 without isolation of the intermediate is described. The prepared terphenyls were found to possess potent anticancer properties against a panel of cancer cells which includes A549, HeLa, MCF7, DU145, HT29 and BxPC-3. Structural similarity with combretastatin A4, these terphenyls disrupted the tubulin polymerization in vitro and destabilized the microtubules in cells. Flow cytometry studies indicated growth arrest of cells in the G2/M phase of the cell cycle corresponding to antimitotic action. Furthermore, compound 4c showed potent anti-mitotic activity even in zebrafish model and could likely be a potential therapeutic compound as it is active both in in vitro and in vivo.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / chemical synthesis
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation
  • Drug Screening Assays, Antitumor
  • Humans
  • Microtubules / drug effects
  • Polymerization / drug effects
  • Structure-Activity Relationship
  • Terphenyl Compounds / chemical synthesis*
  • Terphenyl Compounds / pharmacology*
  • Tubulin / metabolism
  • Zebrafish

Substances

  • Antineoplastic Agents, Phytogenic
  • Terphenyl Compounds
  • Tubulin