Design, synthesis, and anti-proliferative evaluation of [1,1'-biphenyl]-4-ols as inhibitor of HUVEC migration and tube formation

Molecules. 2012 Jul 5;17(7):8091-104. doi: 10.3390/molecules17078091.

Abstract

Allylated biphenol neolignans contain a variety of chemopreventive entities that have been used as anti-tumor drug leads. Herein, 37 allylated biphenols were evaluated for anti-proliferative activity by the MTT assay and inhibitory effect on the migration and tube formation of HUVECs featuring anti-angiogenic properties. 3-(2-Methylbut-3-en-2-yl)-3′,5′-bis(trifluoromethyl)-[1,1′-biphenyl]-4-ol (5c) exerted an inhibitory effect on HUVECs compared to honokiol (IC₅₀ = 47.0 vs. 52.6 μM) and showed significant blocking effects on the proliferation of C26, Hela, K562, A549, and HepG2 (IC₅₀ = 15.0, 25.0, 21.2, 29.5, and 13.0 μM, respectively), superior to those of honokiol (IC₅₀ = 65.1, 62.0, 42.0, 75.0, and 55.4 μM, respectively). Importantly, compound 5c inhibited the migration and capillary-like tube formation of HUVECs in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / chemical synthesis*
  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / pharmacology*
  • Biphenyl Compounds / chemical synthesis*
  • Biphenyl Compounds / chemistry
  • Biphenyl Compounds / pharmacology*
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects
  • HeLa Cells
  • Hep G2 Cells
  • Human Umbilical Vein Endothelial Cells / cytology*
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Humans
  • Inhibitory Concentration 50
  • Neovascularization, Physiologic / drug effects*
  • Structure-Activity Relationship

Substances

  • Angiogenesis Inhibitors
  • Biphenyl Compounds