Multi-substituted N-phenyl-2, 2-dichloroacetamide analogues as anti-cancer drugs: design, synthesis and biological evaluation.
Our earlier research has shown that mono-substituted N-phenyl-2, 2-dichloroacetamide exhibited much higher anti-cancer activity than the lead compound sodium dichloroacetate (DCA). In this paper, a variety of multi-substituted N-phenyl-2, 2-dichloroacetamides were synthesized and biologically evaluated. The results showed that 3, 5-disubstituted N-phenyl-2, 2-dichloroacetamide analogues had satisfactory potency. Among them, N-(3, 5-diiodophenyl)-2, 2-dichloroacetamide had an IC50 of 2.84 micromol x L(-1) against non-small cell lung cancer cell line A549 and could induce cancer cell apoptosis.
Key Laboratory of Bioorganic Phosphorus and Chemical Biology, Ministry of Education, Department of Chemistry, Tsinghua University, Beijing 100084, China.
Tian-Wen
TW
Li
Yong-Chong
YC
Yang
Chang-Mei
CM
Cheng
Dong-Chun
DC
Wang
Ai-Jun
AJ
Lu
Yu-Fen
YF
Zhao
D000081:Acetamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology; D045744:Cell Line, Tumor; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000081:Acetamides; D000970:Antineoplastic Agents; C582742:N-(3,5-diiodophenyl)-2,2-dichloroacetamide; C032619:2,2-dichloroacetamide