title: 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.affiliation: Key laboratory of Bioorganic Phosphorus and Chemical Biology, The Ministry of Education, Department of Chemistry, Tsinghua University, Beijing, 100084, PR China.
authors.forename: Yongchong
authors.initials: Y
authors.lastname: Yang
authors.forename: Peihua
authors.initials: P
authors.lastname: Shang
authors.forename: Changmei
authors.initials: C
authors.lastname: Cheng
authors.forename: Dongchun
authors.initials: D
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Tianwen
authors.initials: T
authors.lastname: Li
authors.forename: Aijun
authors.initials: A
authors.lastname: Lu
authors.forename: Yufen
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D000083:Acetanilides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D015195:Drug Design; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D013329:Structure-Activity Relationship
chemical_list: D000081:Acetamides; D000083:Acetanilides; D000970:Antineoplastic Agents; C032619:2,2-dichloroacetamide