Novel N-phenyl dichloroacetamide derivatives as anticancer reagents: design, synthesis and biological evaluation.

A current study shows that sodium dichloroacetate (DCA) can induce cancer cell apoptosis and inhibit tumor growth, but its cytotoxic activity is low (IC(50) > 1000 microM for A549). In this paper, a variety of DCA derivatives were synthesized, and their cytotoxic activities were evaluated. The result showed that the N-phenyl-2,2-dichloroacetamide analogues had satisfactory potencies. Among them, N-(3-iodophenyl)-2,2-dichloroacetamide (3e), an optimized lead compound, has an IC(50) against A549 as low as 4.76 microM. Furthermore, it can induce cancer cell apoptosis and has a low toxicity in mice (LD(50) = 1117 mg/kg).