AUTHOR=Shi Lingyu , Yang Shanbo , Chang Jing , Zhang Yujing , Liu Wenjing , Zeng Jun , Meng Jingsen , Zhang Renshuai , Wang Chao , Xing Dongming 

TITLE=Design, synthesis and biological evaluation of 9-aryl-5H-pyrido[4,3-b]indole derivatives as potential tubulin polymerization inhibitors

JOURNAL=Frontiers in Chemistry

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2022.1004835

DOI=10.3389/fchem.2022.1004835

ISSN=2296-2646

ABSTRACT=<p>A series of new 9-aryl-5<italic>H</italic>-pyrido[4,3-<italic>b</italic>]indole derivatives as tubulin polymerization inhibitors were designed, synthesized, and evaluated for antitumor activity. All newly prepared compounds were tested for their anti-proliferative activity <italic>in vitro</italic> against three different cancer cells (SGC-7901, HeLa, and MCF-7). Among the designed compounds, compound <bold>7k</bold> displayed the strongest anti-proliferative activity against HeLa cells with IC<sub>50</sub> values of 8.7 ± 1.3 μM. In addition, <bold>7k</bold> could inhibit the polymerization of tubulin and disrupt the microtubule network of cells. Further mechanism studies revealed that <bold>7k</bold> arrested cell cycle at the G2/M phase and induced apoptosis in a dose-dependent manner. Molecular docking analysis confirmed that <bold>7k</bold> may bind to colchicine binding sites on microtubules. Our study aims to provide a new strategy for the development of antitumor drugs targeting tubulin.</p>