Synthesis and Biological Evaluation of Thiabendazole Derivatives as Anti-Angiogenesis and Vascular Disrupting Agents
Bioorganic & Medicinal Chemistry
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.
Zhang, Chao; Zhong, Bo; Yang, Simin; Pan, Liangkun; Yu, Siwang; Li, Zhongjun; Li, Shuchun; Su, Bin; and Meng, Xiangbao, "Synthesis and Biological Evaluation of Thiabendazole Derivatives as Anti-Angiogenesis and Vascular Disrupting Agents" (2015). Chemistry Faculty Publications. 453.