Design, synthesis, and biological evaluation of novel γ-carboline ketones as anticancer agents

A series of novel γ-carboline ketones were designed, synthesized and evaluated for their cytotoxic activity in vitro against six human cancer cell lines (A549, SGC, HCT116, MCF-7, K562 and K562R). Biological evaluation revealed that almost all of the new compounds displayed moderate to potent cytotoxic activities against the tested cells. Among them, seven of the fourteen new compounds show more potent cytotoxic activities against K562R cell line than that of the positive control, taxol. Primary mechanism research on the most potent compound 6f indicated that it was a potent tubulin polymerization inhibitor, with IC 50 value of 4.3 μM, equivalent to that of CA-4, and arresting cell cycle in G 2/M phase. A new series of γ-carboline ketones were designed, synthesized and evaluated for their cytotoxic activities, cell cycle effects, and tubulin polymerization inhibition. [Display omitted] ► We designed and synthesized a new series of γ-carboline ketones. ► All the compounds were tested their cytotoxic activities in vitro against six human cancer cell lines including a multidrug resistant cell. Almost all of the new compounds displayed moderate to potent cytotoxic activities against the tested cells. ► The most potent compound 6f indicated that it was a potent tubulin polymerization inhibitor and arrested cell cycle in G 2/M phase.