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Synthesis and biological evaluation of 1-(4'-Indolyl and 6'-Quinolinyl) indoles as a new class of potent anticancer agents |
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| Authors: | Lai Mei-Jung Chang Jang-Yang Lee Hsueh-Yun Kuo Ching-Chuan Lin Mei-Hsiang Hsieh Hsing-Pang Chang Chi-Yen Wu Jian-Sung Wu Su-Ying Shey Kuang-Shing Liou Jing-Ping |
| Affiliation: | a School of Pharmacy, College of Pharmacy, Taipei Medical University, No. 250, Wuxing Street, Taipei 11031, Taiwan, ROC b National Institute of Cancer Research, National Health Research Institutes, Tainan 70456, Taiwan, ROC c Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli 350, Taiwan, ROC d Division of Hematology and Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 70456, Taiwan, ROC e Department of Obstetrics and Gynecology, Cheng Hsin General Hospital, Taipei, Taiwan, ROC |
| Abstract: | A novel series of the biheterocycles-based compounds with core structure distinguished from combretastatin A-4 (1) and colchicine (5) have been synthesized and evaluated as potent anti-mitotic agents. Compound 1-(4′-Indolyl and 6′-quinolinyl)-4,5,6-trimethoxyindoles 13 and 19 showed substantial anti-proliferative activity against various human cancer cell lines, regardless to the tissue origin and the expression of multiple-drug resistance MDR1, with a mean IC50 value of 38 and 24 nM respectively. Compound 13 (IC50 = 1.7 μM) also exhibited similar anti-tubulin activities to 1 (IC50 = 1.8 μM) and displayed strong binding property to the colchicine binding site on the microtubules. Computational modeling analysis revealed that the binding mechanism of compound 13 is similar to that of CA4. |
| Keywords: | Inhibition of tubulin polymerization Anti-mitotic agent |
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