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

Eur J Med Chem. 2010 Sep;45(9):4300-6. doi: 10.1016/j.ejmech.2010.06.032. Epub 2010 Jun 30.

Abstract

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / chemical synthesis
  • Acetamides / chemistry*
  • Acetamides / pharmacology*
  • Acetamides / toxicity
  • Acetanilides / chemical synthesis
  • Acetanilides / chemistry*
  • Acetanilides / pharmacology*
  • Acetanilides / toxicity
  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / toxicity
  • Cell Line, Tumor
  • Drug Design*
  • Female
  • Humans
  • Inhibitory Concentration 50
  • Lethal Dose 50
  • Male
  • Mice
  • Structure-Activity Relationship

Substances

  • Acetamides
  • Acetanilides
  • Antineoplastic Agents
  • 2,2-dichloroacetamide