Furanylazaindoles: Potent Anticancer Agents in Vitro and in Vivo
| Autor: | Jing Ping Liou, Min Chieh Su, Su Ying Wu, Samir Mehndiratta, Chih Ying Nien, Hsueh Yun Lee, Ching Chuan Kuo, Shiow Lin Pan, Mei Jung Lai, Chi Yen Chang, Jian Sung Wu, Jang Yang Chang, Yi Min Liu, Yi Ting Chang |
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| Rok vydání: | 2013 |
| Předmět: |
Indoles
Cell cycle checkpoint Cell Survival Mice Nude Antineoplastic Agents Pharmacology Heterocyclic Compounds 2-Ring Polymerization Inhibitory Concentration 50 Tubulin In vivo Cell Line Tumor Neoplasms Drug Discovery Animals Humans Bioassay Cytotoxicity Cell Proliferation Sulfonamides Dose-Response Relationship Drug Molecular Structure biology Chemistry Cell growth Cell Cycle Checkpoints Cell cycle Xenograft Model Antitumor Assays In vitro Drug Design biology.protein Molecular Medicine Female HT29 Cells |
| Zdroj: | Journal of Medicinal Chemistry. 56:8008-8018 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm4011115 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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