Discovery of novel N-alkyl 4-anilinofuro[2,3-b]quinoline derivatives (CIL-102 derivatives) against castration-resistant human prostate cancers

We Fen Lo, Yu Wei Chou, Chih Hua Tseng, Yia Huei Shiu, Yu Wen Chen, Shyh Chyun Yang, Yeh Long Chen, Ming Fong Lin, Cherng Chyi Tzeng

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3 Scopus citations


A number of N-alkylated 4-anilinofuro[2,3-b]quinoline derivatives were synthesized and evaluated in vitro against PC-3, A549, and MCF-7 cancer cells and M-10 normal human mammary epithelial cells. The known antimitotic CIL-102 was moderately active against the growth of PC-3 prostate cancer cells with an IC50value of 2.69 μM; while it was more potent against the growth of A549, MCF-7 and M-10 cells with IC50values of 0.61, 0.31 and 0.95 μM, respectively. However, the cytotoxic profiles of its N-alkylated derivatives, 6a - 6c, were reversed and strongly inhibited PC-3 cell growth with IC50values of less than 1.0 μM but only weakly against the growth of A549, MCF-7 and M-10 cells. These results indicated that N-alkylation of CIL-102 increased not only selectivity but also the antiproliferative potency against PC-3 cell growth. Among these derivatives synthesized, N-(4-acetylphenyl)-N-(furo[2,3-b]quinolin- 4-yl)methylamine (6a) and its N-ethyl counterpart 6b are the two most active CIL-102 derivatives against PC-3 cell growth with IC50value of 0.22 and 0.20 μM, respectively. Compound 6a is less cytotoxic to normal human M-10 cells than 6b and therefore was selected for further mechanism studies. The flow cytometry studies clearly indicated that compound 6a induced cell accumulation in G2/M phase in a dose-dependent manner after 24 h-treatment. While the proliferation of LNCaP C-81 prostate cancer cells was also strongly suppressed by compound 6a; compound 11a exhibited better selective activity toward LNCaP C-81 prostate cancer cells over RWPE-1 non-cancerous prostate epithelia. Thus, this group of compounds has a potential of serving as therapeutic agents toward advanced castration-resistant prostate cancers.

Original languageEnglish (US)
Pages (from-to)493-500
Number of pages8
JournalAnti-Cancer Agents in Medicinal Chemistry
Issue number4
StatePublished - May 1 2015



  • Anticancer activity
  • CIL-102
  • LNCaP C-81
  • N-alkylated 4-anilinofuro[2,3-b]quinoline derivatives
  • PC-3

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Cancer Research

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