Design, synthesis and biological evaluation of 3′,4′,5′-trimethoxy flavonoid benzimidazole derivatives as potential anti-tumor agents

Abstract

A series of 3',4',5'-trimethoxy flavonoids with benzimidazole linked by different chain alkanes have been designed and synthesized. The potential activity of these compounds as anti-tumor agents was evaluated by cytotoxicity assay in MGC-803 (human gastric cancer), MCF-7 (human breast cancer), HepG-2 (human hepatoma) and MFC (mouse gastric cancer) tumor cell lines. Among them, compound <b>15</b> 7-(3-(2-chloro-1<i>H</i>-benzo[<i>d</i>]imidazol-1-yl)propoxy)-2-(3,4,5-trimethoxyphenyl)-4<i>H</i>-chromen-4-one displayed the most potent antiproliferative activity, with IC₅₀ values of 20.47 ± 2.07, 43.42 ± 3.56, 35.45 ± 2.03 μM and 23.47 ± 3.59 μM, respectively. The flow cytometry (FCM) results showed that compound <b>15</b> caused the cell cycle to be arrested in G1 phase and induced apoptosis of MFC cells in a dose-dependent manner. In addition, compound <b>15</b> exhibited a significant inhibitory effect on tumor growth <i>in vivo</i>. All the results outlined the great potential of compound <b>15</b> for further exploitation as anti-tumor agent.