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    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/30961


    標題: Synthesis and Antitumor Properties of BQC-Glucuronide, a Camptothecin Prodrug for Selective Tumor Activation
    作者: Prijovich, Zeljko M.
    Burnouf, Pierre-Alain
    Chou, Hua-Cheng
    Huang, Ping-Ting
    Chen, Kai-Chuan
    Cheng, Tian-Lu
    Leu, Yu-Lin
    Roffler, Steve R.
    貢獻者: Acad Sinica, Inst Biomed Sci, Acad Rd
    Natl Yang Ming Univ, Taiwan Int Grad Program Mol Med
    Acad Sinica, Acad Rd
    Kaohsiung Med Univ, Fac Biomed Sci & Environm Biol
    Chia Nan Univ
    關鍵字: camptothecin
    glucuronide
    prodrug
    cancer
    targeted therapy
    beta-glucuronidase
    albumin influence
    ADEPT
    metastasis
    日期: 2016-04
    上傳時間: 2018-01-18 11:38:46 (UTC+8)
    出版者: Amer Chemical Soc
    摘要: Major limitations of camptothecin anticancer drugs (toxicity, nonselectivity, water insolubility, inactivation by human serum albumin) may be improved by creating glucuronide prodrugs that rely on beta-glucuronidase for their activation. We found that the camptothecin derivative 5,6dihydro-4H-benzo [de] quinoline-camptothecin (BQC) displays greater cytotoxicity against cancer cells than the clinically used Norma tissue camptothecin derivatives SN-38 and topotecan even in the presence of human serum albumin. We synthesized the prodrug BQC-glucuronide (BQC-G), which was 4000 times more water soluble and 20-40 times less cytotoxic than BQC. Importantly, even in the presence of human serum albumin, BQC-G was efficiently hydrolyzed by beta-glucuronidase and produced greater cytotoxicity (IC50 = 13 nM) than camptothecin, 9-aminocamptothecin, SN-38, or topotecan (IC50 > 3000, 1370, 48, and 28 nM, respectively). BQC-G treatment of mice bearing human colon cancer xenografts with naturally or artificially elevated beta-glucuronidase activity produced significant antitumor activity, showing that BQC-G is a potent prodrug suitable for selective intratumoral drug activation.
    關聯: Molecular Pharmaceutics, v.13 n.4, pp.1242-1250
    Appears in Collections:[藥學系(所)] 期刊論文

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