Synthesis and biological evaluation of thiabendazole derivatives as anti-angiogenesis and vascular disrupting agents

Bioorg Med Chem. 2015 Jul 1;23(13):3774-80. doi: 10.1016/j.bmc.2015.03.085. Epub 2015 Apr 8.

Abstract

Thiabendazole, already approved by FDA for oral use as an anti-fungal and anti-helminthic drug since 1967, has recently been repurposed as a vascular disrupting agent. By optimization of the structure of the lead compound, we successfully identified compound TBZ-19 and the new derivative is over 100-fold more potent than the lead compound against the growth of four different cell lines (A549, HCT-116, HepG2 and HUVECs). The most potent two candidates TBZ-07 and TBZ-19, exhibiting moderate inhibitory cell proliferation activity, were also verified as anti-angiogenesis and vascular disrupting agents. Therefore, TBZ-07 and TBZ-19 would be promising candidates with vasculature targeting activity and merit further development.

Keywords: Anti-angiogenesis; Anti-cancer; Thiabendazole; Tubulin; Vascular targeting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / chemical synthesis*
  • Angiogenesis Inhibitors / pharmacology
  • Anthelmintics / chemical synthesis
  • Anthelmintics / pharmacology
  • Cell Proliferation / drug effects
  • Drug Repositioning
  • HCT116 Cells
  • Hep G2 Cells
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Structure-Activity Relationship
  • Thiabendazole / analogs & derivatives*
  • Thiabendazole / chemical synthesis*
  • Thiabendazole / pharmacology
  • Tubulin / chemistry
  • Tubulin / metabolism
  • Tubulin Modulators / chemical synthesis*
  • Tubulin Modulators / pharmacology

Substances

  • Angiogenesis Inhibitors
  • Anthelmintics
  • Tubulin
  • Tubulin Modulators
  • Thiabendazole