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

• Published in: European journal of medicinal chemistry 2010-09, Vol.45 (9), p.4300-4306
• Main Authors: Yang, Yongchong, Shang, Peihua, Cheng, Changmei, Wang, Dongchun, Yang, Ping, Zhang, Feng, Li, Tianwen, Lu, Aijun, Zhao, Yufen
• Format: Article
• Language: English
• Subjects: Acetamides - chemical synthesis; Acetamides - chemistry; Acetamides - pharmacology; Acetamides - toxicity; Acetanilides - chemical synthesis; Acetanilides - chemistry; Acetanilides - pharmacology; Acetanilides - toxicity; Animals; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antineoplastic Agents - toxicity; Apoptosis; Biological and medical sciences; Cell Line, Tumor; Cytotoxic activity; Drug Design; Female; General aspects; Humans; Inhibitory Concentration 50; Lethal Dose 50; Male; Medical sciences; Mice; N-phenyl dichloroacetamide; Pharmacology. Drug treatments; Sodium dichloroacetate (DCA); Structure-Activity Relationship
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2010.06.032

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 μM 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 μM. Furthermore, it can induce cancer cell apoptosis and has a low toxicity in mice (LD 50 = 1117 mg/kg). N-phenyl-2,2-dichloroacetamide analogues has higher cytotoxic activity and N-(3-iodophenyl)-2,2-dichloroacetamide ( 3e) is an optimized lead compound. [Display omitted]