Furanylazaindoles: Potent anticancer agents in vitro and in vivo

Hsueh Yun Lee, Shiow Lin Pan, Min-Chieh Su, Yi-Min Liu, Ching-Chuan Kuo, Yi-Ting Chang, Jian-Sung Wu, Chih-Ying Nien, Samir Mehndiratta, Chi-Yen Chang, Su-Ying Wu, Mei-Jung Lai, Jang-Yang Chang, Jing Ping Liou

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Preliminary biological data on 7-anilino-6-azaindoles (8-11) suggested that hydrophobic substituents at C7 contribute to enhancement of antiproliferative activity. A novel series of 7-aryl-6-azaindole-1-benzenesulfonamides (12-22) were developed and showed improved cytotoxicity compared to ABT751 (5). The conversion of C7 phenyl rings into C7 heterocycles led to a remarkable improvement of antiproliferative activity. Among all the synthetic products, 7-(2-furanyl)-1-(4-methoxybenzenesulfonyl)-6-azaindole (21) exhibited the most potent anticancer activity against KB, HT29, MKN45, and H460 cancer cell lines with IC50 values of 21.1, 32.0, 27.5, and 40.0 nM, respectively. Bioassays indicated that 21 not only inhibits tubulin polymerization by binding to tubulin at the colchicine binding site but also arrests the cell cycle at the G2/M phase with slight arrest at the sub-G1 phase. Compound 21 also functions as a vascular disrupting agent and dose-dependently inhibits tumor growth without significant change of body weight in an HT29 xenograft mouse model. Taken together, compound 21 has potential for further development as a novel class of anticancer agents.

Original languageEnglish
Pages (from-to)8008-8018
Number of pages11
JournalJournal of Medicinal Chemistry
Volume56
Issue number20
DOIs
Publication statusPublished - 2013

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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  • Cite this

    Lee, H. Y., Pan, S. L., Su, M-C., Liu, Y-M., Kuo, C-C., Chang, Y-T., Wu, J-S., Nien, C-Y., Mehndiratta, S., Chang, C-Y., Wu, S-Y., Lai, M-J., Chang, J-Y., & Liou, J. P. (2013). Furanylazaindoles: Potent anticancer agents in vitro and in vivo. Journal of Medicinal Chemistry, 56(20), 8008-8018. https://doi.org/10.1021/jm4011115