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.
Chao Zhang  1 ,  Bo Zhong  2 ,  Simin Yang  1 ,  Liangkun Pan  1 ,  Siwang Yu  1 ,  Zhongjun Li  1 ,  Shuchun Li  1 ,  Bin Su  2 ,  Xiangbao Meng  3
Affiliations
  • 1. State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
  • 2. Department of Chemistry, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH 44115, USA.
  • 3. State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address: [email protected].
PMID: 25936258 DOI: 10.1016/j.bmc.2015.03.085
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.