Yin Yong, Qiao Fang, Jiang Lu-Yi, Wang She-Feng, Sha Shao, Wu Xun, Lv Peng-Cheng, Zhu Hai-Liang
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
Bioorg Med Chem. 2014 Aug 1;22(15):4285-92. doi: 10.1016/j.bmc.2014.05.029. Epub 2014 May 21.
A series of novel (E)-3-(3,4-dihydroxyphenyl)acrylylpiperazine derivatives had been synthesized and evaluated their biological activities as potential tubulin polymerization inhibitors. Among these compounds, compound 3q exhibited potent antiproliferative activities against three cancer cell lines in vitro, and antitubulin polymerization activity with IC₅₀ of 0.92 μM, which was superior to that of colchicine (IC₅₀=1.34 μM). Docking simulation was performed to insert compound 3q into the crystal structure of tubulin at colchicine binding site to determine the probable binding model. These results suggested that compound 3q may be a promising antitubulin agent for the potential treatment of cancer.
一系列新型（E）-3-（3,4-二羟基苯基）丙烯酰哌嗪衍生物已被合成，并评估了它们作为潜在微管蛋白聚合抑制剂的生物活性。在这些化合物中，化合物3q在体外对三种癌细胞系表现出强大的抗增殖活性，以及微管蛋白聚合抑制活性，IC₅₀为0.92 μM，优于秋水仙碱（IC₅₀ = 1.34 μM）。进行对接模拟，将化合物3q插入秋水仙碱结合位点的微管蛋白晶体结构中，以确定可能的结合模式。这些结果表明，化合物3q可能是一种有前景的抗微管蛋白药物，有望用于癌症治疗。
