As part of our continuing search for potential anticancer drug candidates in the 2-phenyl-1, 8-naphthyridin-4-one (2PN), we had synthesized a series of 5, 6, 7, 2', 3', 4'-substituted 2-phenyl-1, 8-naphthyridin-4 (1H)-one derivatives and examined their anticancer effects and further investigated their action mechanism. Human cancer cells were cultured with synthesized compounds or vehicles. The cytotoxic effects were determined by MTT assay for 48 h. Furthermore, the action mechanisms were determined by using cell cycle analysis, DNA fragmentation, Western blot and RT-PCR technology. Among the synthesized compounds, we found that 5-methyl-2-(2'-fluorophenyl)- 1,8-naphthyridin-4-one (LYF-17) is a more effective compound, and it was more sensitive to leukemia HL-60 cells with IC50 values of approximately 44.4 nM. LYF-17 may exert its anticancer action by inducing cell cycle G2/M arrest and promoting cell apoptosis. This finding suggests that LYF-17 may have potential to be a novel anticancer agent.?
