a novel synthetic analog of 5, 8-disubstituted quinazolines blocks mitosis and induces apoptosis of tumor cells by inhibiting microtubule polymerization一种新型合成模拟的8-disubstituted喹唑啉块肿瘤细胞的有丝分裂和凋亡抑制微管聚合.pdfVIP

A Novel Synthetic Analog of 5, 8-Disubstituted Quinazolines Blocks Mitosis and Induces Apoptosis of Tumor Cells by Inhibiting Microtubule Polymerization 2 2 1 1 1 1 1 2 1 Wei Tian , Lili Qin , Qiaoling Song , Li He , Midan Ai , Yi Jin , Zuyu Zhou , Song You , Yaqiu Long , Qiang Yu1* 1 Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China, 2 The School of Life Science and Biopharmaceutics of Shenyang Pharmaceutical University, Liaoning, China Abstract Many mitosis inhibitors are powerful anticancer drugs. Tremendous efforts have been made to identify new anti-mitosis compounds for developing more effective and less toxic anti-cancer drugs. We have identified LJK-11, a synthetic analog of 5, 8-disubstituted quinazolines, as a novel mitotic blocker. LJK-11 inhibited growth and induced apoptosis of many different types of tumor cells. It prevented mitotic spindle formation and arrested cells at early phase of mitosis. Detailed in vitro analysis demonstrated that LJK-11 inhibited microtubule polymerization. In addition, LJK-11 had synergistic effect with another microtubule inhibitor colchicine on blocking mitosis, but not with vinblastine or nocodazole. Therefore, LJK-11 represents a novel anti-microtubule structure. Understanding the function and mechanism of LJK-11 will help us to better understand the action of anti-microtubule agents and to design better anti-cancer drugs. Citation: Tian W, Qin L, Song Q, He L, Ai M, et al. (2010) A Novel Synthetic Analog of 5, 8-Disubstituted Quinazolines Blocks Mitosis and Induces Apoptosis of Tumor Cells by Inhibiting Microtubule Polymerization. PLoS ONE 5(5): e10499. doi:10.1371/journal.pone.0010499 Editor: Eric J. Bernhard, National Cancer Institute,