کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1366229 981585 2007 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Structure–activity studies of phenanthroindolizidine alkaloids as potential antitumor agents
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Structure–activity studies of phenanthroindolizidine alkaloids as potential antitumor agents
چکیده انگلیسی

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 GI50s of DCB-3503 and PA-7 were 35 ± 5 nM and 11 ± 5 nM, 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-κB-inhibitory effects and their cyclin D1 down-regulatory effects.

Structure–activity relationships were explored based on a series of phenanthroindolizidine alkaloids synthesized or isolated. DCB-3503 and PA-7 (tylophorinidine) were determined to be the most active compounds against HepG2 tumor growth both in vitro and in vivo.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 17, Issue 15, 1 August 2007, Pages 4338–4342
نویسندگان
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