Design, synthesis and biological evaluation of isoxazole-naphthalene derivatives as anti-tubulin agents

Arabian Journal of Chemistry

Wenjing Liu¹  Yongjun Li²  Yong Huang³  Zhiyun Peng⁴  Guangcheng Wang⁴ 

[1] College of Chemistry and Chemical Engineering, Jishou University, Jishou, China;College of Food Science and Technology, Shanghai Ocean University, Shanghai, China (Z. Peng).;Corresponding authors at: State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, China (G. Wang);State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, China;

关键词: Isoxazole;    Naphthalene;    Anti-tubulin agents;    Tubulin polymerization;    Antitumor;   

DOI  :  

来源: DOAJ

【 摘 要 】

In this study, a novel series of isoxazole-naphthalene derivatives as tubulin polymerization inhibitors were designed, synthesized and evaluated for their anti-proliferative activities against human breast cancer cell line MCF-7. Most of the synthesized compounds exhibited moderate to potent antiproliferative activity (IC50 < 10.0 μM), as compared to cisplatin (15.24 ± 1.27 μM). Among them, compound 5j containing 4-ethoxy substitution at phenyl ring was found to be the most active compound with IC50 value of 1.23 ± 0.16 μM. Mechanistic studies revealed that compound 5j arrested cell cycle at G2/M phase and induces apoptosis. Furthermore, in vitro tubulin polymerization assay showed that compound 5j displayed better inhibition activity on tubulin polymerization (IC50 = 3.4 μM) than colchicine (IC50 = 7.5 μM). Molecular docking study also revealed that compound 5j binds to the colchicine binding site of tubulin.

【 授权许可】

Unknown