Synthesis and biological evaluation of 4-biphenylamino-5-halo-2(5H)-furanones as potential anticancer agents.

An efficient route without metal catalyst has been developed for synthesis of 4-biphenylamino-5-halo-2(5H)-furanones. The antitumor activities against various tumor cells of all the compounds have been evaluated by MTT assay. Among them, the compound 3j exhibits significant inhibitory activity against MCF-7 human breast cancer cells with an IC50 value of 11.8 μM and low toxicity toward HaCaT human normal cells. The mechanism studies confirm that 3j can induce cell cycle arrest at G2/M phase in MCF-7 cells. Compared with compound 3e, 3j has stronger binding affinity to c-myc G-quadruplex (G4) DNA via π-π stacking and H-bonding interactions. Western blot analysis also further confirms that compound 3j can down-regulate the expression of c-myc in MCF-7 cells.