Design,synthesis and biological evaluation of novel indolin-2-ones as potent anticancer compounds |
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| Authors: | Andong Zhou Lei Yan Fangfang Lai Xiaoguang Chen Masuo Goto Kuo-Hsiung Lee Zhiyan Xiao |
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| Institution: | 1. Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China;2. Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China;3. Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7568, USA;4. Chinese Medicine Research and Development Center, China Medical University and Hospital, Taichung, Taiwan |
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| Abstract: | The indolin-2-one core is a privileged structure for antitumor agents, especially kinase inhibitors. Twenty-three novel indolin-2-ones were designed by molecular dissection of the anticancer drug indirubin. Seventeen of them exhibited significant inhibition against the tested cell lines, and two of them (1c and 1h) showed IC50 values at the submicromolar level against HCT-116 cells. Compounds 1c and 2c were also potent inhibitors of the triple-negative breast cancer (TNBC) cell line MDA-MB-231. Flow cytometry was utilized to explore the antitumor mechanism of 1c and 2c with MDA-MB-231 cells, and distinct effects were observed on 2c. Furthermore, immunocytochemical examination of 1c suggested a destabilization of microtubules, which was significantly different from the effect of IM, an indirubin derivative. |
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| Keywords: | Indolin-2-one Privileged structure Cytotoxicity Molecular mechanism |
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