Structure-activity studies of phenanthroindolizidine alkaloids as potential antitumor agents
Structure-activity studies of phenanthroindolizidine alkaloids as potential antitumor agents
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DOI：
10.1016/j.bmcl.2007.05.021
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发表时间：
2007-08-01
影响因子：
2.7
通讯作者：
Cheng, Yung-Chi
中科院分区：
文献类型：
--
作者：
Gao, Wenli;Bussom, Scott;Cheng, Yung-Chi
化学合成了5个phenanthroindolizidine生物碱（PA），并从褐蝗中分离得到7个。为了进一步开发出具有抗肿瘤潜力的吩anthroindolizidine类生物碱，我们对这类化合物的构效关系进行了研究。我们证明DCB-3503和tylophorinidine （PA-7）是体外和体内抗肿瘤生长最有效的化合物。在肝癌细胞系HepG2中，DCB-3503和PA-7的GI(50)S分别为35 +/- 5 nM和11 +/- 5 nNI。DCB-3503和PA-7腹腔注射剂量为9 mg/kg，每天2次，每3天1次，共4个周期（P < 0.05， PA-7组P < 0.01），可显著抑制裸鼠HepG2肿瘤的生长。它们的抗肿瘤活性与其nf - κ b抑制作用和cyclin D1下调作用相关。(c) 2007 Elsevier Ltd.版权所有。
Five phenanthroindolizidine alkaloids (PA) were chemically synthesized and seven were isolated from Tylophora atrofolliculata. To facilitate future drug design of phenanthroindolizidine alkaloids as potential antitumor agents, we have explored the structure-activity relationships (SAR) of this class of compounds. We demonstrated that DCB-3503 and tylophorinidine (PA-7) were among the most active compounds against tumor growth both in vitro and in vivo. In the hepatocellular carcinoma cell line HepG2, the GI(50)S of DCB-3503 and PA-7 were 35 +/- 5 nM and 11 +/- 5 nNI, respectively. DCB-3503 and PA-7 significantly inhibited HepG2 tumor growth in nude mice at a dose of 9 mg/kg given by intraperitoneal (ip) injections twice a day every third day for a total of four cycles (P < 0.05 for DCB-3503 and P < 0.01 for PA-7). Their potent antitumor activities correlated with their potent NF-kappa B-inhibitory effects and their cyclin D1 down-regulatory effects. (c) 2007 Elsevier Ltd. All rights reserved.