Synthesis and Biological Evaluation of Thiabendazole Derivatives as Anti-Angiogenesis and Vascular Disrupting Agents

Document Type

Article

Publication Date

7-1-2015

Publication Title

Bioorganic & Medicinal Chemistry

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.

Comments

We gratefully acknowledge the National Natural Science Foundation of China (NSFC No. 81273370) for generous financial support.

DOI

10.1016/j.bmc.2015.03.085

Volume

23

Issue

13

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