Design and synthesis of diarylamines and diarylethers as cytotoxic antitumor agents

Xiao Feng Wang, Xing Tao Tian, Emika Ohkoshi, Bingjie Qin, Yi Nan Liu, Pei Chi Wu, Mann Jen Hour, Hsin Yi Hung, Keduo Qian, Rong Huang, Kenneth F. Bastow, William P. Janzen, Jian Jin, Susan L. Morris-Natschke, Kuo Hsiung Lee, Lan Xie

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)


Based on a shared structural core of diarylamine in several known anticancer drugs as well as a new cytotoxic hit 6-chloro-2-(4-cyanophenyl)amino- 3-nitropyridine (7), 30 diarylamines and diarylethers were designed, synthesized, and evaluated for cytotoxic activity against A549, KB, KB-vin, and DU145 human tumor cell lines (HTCL). Four new leads 11e, 12, 13a, and 13b were discovered with GI50 values ranging from 0.33 to 3.45 μM. Preliminary SAR results revealed that a diarylamine or diarylether could serve as an active structural core, meta-chloro and ortho-nitro groups on the A-ring (either pyridine or phenyl ring) were necessary and crucial for cytotoxic activity, and the para-substituents on the other phenyl ring (B-ring) were related to inhibitory selectivity for different tumor cells. In an investigation of potential biological targets of the new leads, high thoughput kinase screening discovered that new leads 11e, 12 and 13b especially inhibit Mer tyrosine kinase, a proto-oncogene associated with munerous tumor types, with IC50 values of 2.2-3.0 μM. Therefore, these findings provide a good starting point to optimize a new class of compounds as potential anticancer agents, particularly targeting Mer tyrosine kinase.

Original languageEnglish
Pages (from-to)6224-6228
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Issue number19
Publication statusPublished - 2012 Oct 1

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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