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    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/27609


    標題: Synthesis of 6-substituted 9-methoxy-11H-indeno[1,2-c]quinoline-11-one derivatives as potential anticancer agents
    作者: Tseng, Chih-Hua
    Chen, Yeh-Long
    Yang, Chiao-Li
    Cheng, Chih-Mei
    Han, Chein-Hwa
    Tzeng, Cherng-Chyi
    Tzeng, Cherng-Chyi�
    貢獻者: 藥學系
    關鍵字: Anticancer Agents
    Indeno[1,2-C]Quinolinone Derivatives
    Cell Cycle Arrest
    Apoptosis
    日期: 2012-07-15
    上傳時間: 2014-03-21 16:15:08 (UTC+8)
    出版者: Pergamon-Elsevier Science Ltd
    摘要: We have synthesized certain 6-substituted 9-methoxy-11H-indeno[1,2-c]quinolin-11-ones for antiproliferative evaluation. Results indicated that 6-alkylamine derivatives, 6-[2-(dimethylamino)ethylamino]-9methoxy-11H-indeno[1,2-c]quinolin-11-on e (5a) and its 6-[3-(dimethylamino)propylamino]derivative, 5b, were able to inhibit cells growth completely at a concentration of 100 mu M while most of the 6-arylamine derivatives 6b-6h were inactive at the same concentration. Comparable mean GI(50) (drug molar concentration causing 50% cell growth inhibition) values for 5a (3.47 mu M) and 5b (3.39 mu M) indicated the cytotoxicity may not be affected by the length of alkyl substituents at C-6 position. Compound 5b, with a mean GI(50) value of 3.39 mu M, was the most active and therefore was selected for further evaluation on its effects of H460 lung cancer cell cycle distribution. Results indicated that 5b induced cell cycle arrest in G2/M phase after 24 h treatment, while the hypodiploid (sub-G0/G1 phase) cells increased. We found that H460 cell became shrinked after the treatment of 5b, indicating that apoptosis may be a mechanism by which 5b kills the cancer cells. DNA unwinding assay indicated that 5b may bind to DNA through intercalation. Our results have also demonstrated that PARP was cleaved while caspase-3 and caspase-8 activities were induced after the treatment of 5b at 10 mu M for 24 h. Thus, compound 5b intercalates DNA, induces cell cycle arrest at G2/M phase via cleavage of PARP, induces caspase-3 and caspase-8 activities, and consequently causes the cell death. (C) 2012 Elsevier Ltd. All rights reserved.
    關聯: Bioorganic & Medicinal Chemistry, 20(14), 4397-4404
    Appears in Collections:[藥學系(所)] 期刊論文

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