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

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).

• Authors: Yongchong Yang, Peihua Shang, Changmei Cheng, Dongchun Wang, Ping Yang, Feng Zhang, Tianwen Li, Aijun Lu, Yufen Zhao
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 45 Issue 9 Pg. 4300-6 (Sep 2010) ISSN: 1768-3254 [Electronic] France
• PMID: 20663593 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2010 Elsevier Masson SAS. All rights reserved.

Chemical References

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

Topics

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