Purpose: As part of our continuing search for potential anticancer drug candidates in the 2-phenyl-4-quinolone series, we have synthesized 3', 6-substituted 2-phenyl-4-quinolone-3-carboxylic acid derivatives and examined their antitumor effects to be established structure activity relationships. Methods: Human leukemia cells were cultured with 3', 6-substituted 2-phenyl-4-quinolone-3-carboxylic acid derivatives or vehicles. The cytotoxic effects were determined by MTT assay. Antitumor mechanisms were determined by using cell cycle analysis, DNA fragmentation, and RT-PCR technology. Results: Among the newly synthesized compounds, we found that 3'-fluoro-6-methoxy-2-phenyl-4-quinolone-3-carboxylic acid (12-3) is most effective against HL-60 cells with IC50 values of approximately 0.75μM. Furthermore, 12-3 may exert its antitumor action by inducing cell cycle G2/M arrest and promoting cell apoptosis. Conclusions: This finding suggests that compound 12-3 may have potential to be a novel anticancer agent.
