Zhang Chao, Zhong Bo, Yang Simin, Pan Liangkun, Yu Siwang, Li Zhongjun, Li Shuchun, Su Bin, Meng Xiangbao
State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Department of Chemistry, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH 44115, USA.
Bioorg Med Chem. 2015 Jul 1;23(13):3774-80. doi: 10.1016/j.bmc.2015.03.085. Epub 2015 Apr 8.
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.
噻苯达唑自1967年起已被美国食品药品监督管理局（FDA）批准口服用作抗真菌和抗蠕虫药物，最近被重新用作血管破坏剂。通过对先导化合物结构的优化，我们成功鉴定出化合物TBZ-19，这种新衍生物对四种不同细胞系（A549、HCT-116、HepG2和人脐静脉内皮细胞）生长的抑制作用比先导化合物强100倍以上。两种最有效的候选物TBZ-07和TBZ-19表现出适度的抑制细胞增殖活性，也被证实具有抗血管生成和血管破坏作用。因此，TBZ-07和TBZ-19有望成为具有血管靶向活性的候选物，值得进一步开发。
