Synthesis and biological evaluation of thiabendazole derivatives as anti-angiogenesis and vascular disrupting agents.
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.
State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Chao
C
Zhang
Department of Chemistry, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH 44115, USA.
Bo
B
Zhong
State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Simin
S
Yang
State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Liangkun
L
Pan
State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Siwang
S
Yu
State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Zhongjun
Z
Li
State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Shuchun
S
Li
Department of Chemistry, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH 44115, USA.
Bin
B
Su
State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address: xbmeng@bjmu.edu.cn.
Xiangbao
X
Meng
D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D000871:Anthelmintics / Q000138:chemical synthesis / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D058492:Drug Repositioning; D045325:HCT116 Cells; D056945:Hep G2 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D013329:Structure-Activity Relationship; D013827:Thiabendazole / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000494:pharmacology
D020533:Angiogenesis Inhibitors; D000871:Anthelmintics; D014404:Tubulin; D050257:Tubulin Modulators; D013827:Thiabendazole
Anti-angiogenesis; Anti-cancer; Thiabendazole; Tubulin; Vascular targeting