https://scholars.lib.ntu.edu.tw/handle/123456789/544442
標題: | Synthesis and biological evaluation of 2′,5′-dimethoxychalcone derivatives as microtubule-targeted anticancer agents | 作者: | Tu H.-Y. Huang A.-M. Hour T.-C. Yang S.-C. YEONG-SHIAU PU Lin C.-N. |
關鍵字: | Anti-mitotic; Anticancer; Chalcone; Claisen-Schmidt condensation; Microtubule; Paclitaxel; Synthesis; Tubulin polymerization | 公開日期: | 2010 | 卷: | 18 | 期: | 6 | 起(迄)頁: | 2089-2098 | 來源出版物: | Bioorganic and Medicinal Chemistry | 摘要: | A series of novel 2′,5′-dimethoxylchalcone derivatives including 18 new compounds were synthesized and evaluated for cytotoxicities against two human cancer cell lines, NTUB1 (human bladder cancer cell line) and PC3 (human prostate cancer cell line). All these derivatives except for 21 exhibited significant cytotoxic effect against NTUB1 and PC3 cell lines. Compounds 13 and 17 with 4-carbamoyl moiety showed potent inhibitory effect on growth of NTUB1 and PC3 cells. Flow cytometric analysis demonstrated that treatment of NTUB1 cells with 1 μM 13 and 17 induced G1 phase arrest accompanied by an increase in apoptotic cell death of NTUB1 cells after 24 h. Treatment of PC3 cells with 1 μM and 3 μM 13, and 1 μM and 3 μM 17 induced S and G1, and G1 and G2/M phase arrests, respectively, accompanied by an increase in apoptotic cell death. These data suggested that 13 and 17 with different 4-carbamoyl moiety displayed same cell cycle arrest in NTUB1 cells while different doses of 13 and 17 revealed different cell cycle arrest in PC3 cells. Cell morphological study of 17 indicated that more cells rounding up or dead associated with tubulin polymerization. Compound 17 showed an increased α-tubulin level in polymerized microtubule fraction in a dose-dependent manner while 500 nM paclitaxel also showed similar effect in NTUB1 cells by Western blot analysis. The result suggested that 17 may be used as microtubule-targeted agents. ? 2010 Elsevier Ltd. All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-77649231931&doi=10.1016%2fj.bmc.2010.02.012&partnerID=40&md5=1a02f54d342882bc0f569e2dcfe2f4f7 https://scholars.lib.ntu.edu.tw/handle/123456789/544442 |
ISSN: | 0968-0896 | DOI: | 10.1016/j.bmc.2010.02.012 | SDG/關鍵字: | 2',5' dimethoxychalcone derivative; 4 (2 methylethyl)carbamoyl 2',5' dimethoxychalcone; 4 tetrahydropyrrolylcarbamoyl 2',5' dimethoxychalcone; antineoplastic agent; chalcone derivative; cisplatin; unclassified drug; antineoplastic activity; article; cancer cell culture; cancer inhibition; cell cycle regulation; controlled study; drug synthesis; drug targeting; human; human cell; microtubule; reaction analysis; Antineoplastic Agents; Cell Cycle; Cell Proliferation; Cell Survival; Chalcones; Drug Screening Assays, Antitumor; Humans; Microtubules; Structure-Activity Relationship; Tumor Cells, Cultured |
顯示於: | 醫學系 |
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