کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1358409 981340 2013 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Synthesis and mechanistic studies of novel spin-labeled combretastatin derivatives as potential antineoplastic agents
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Synthesis and mechanistic studies of novel spin-labeled combretastatin derivatives as potential antineoplastic agents
چکیده انگلیسی

Two series (14a–d and 21a–h) of novel spin-labeled combretastatin derivatives were synthesized and evaluated for cytotoxicity against four tumor cell lines (K562, SGC-7901, Hela and HepG-2). Simultaneously, a representative compound 21a was selected to investigate the antitumor mechanisms of these synthetic compounds. The results indicated that some of the compounds showed significant cytotoxicity against four tumor cell lines in vitro and were more active than etoposide, a clinically available anticancer drug. Among the newly synthesized compounds, 21a, 21b and 21c displayed the greatest cytotoxicity against three tested tumor cell lines (HEPG-2, BGC-832 and Hela), with IC50 values ranging from 0.15 to 1.05 μM, compared with values of 0.014–0.403 μM for 3-amino-deoxycombretastatin A-4 (3). In addition, the mechanistic analysis revealed that compound 21a effectively interfered with tubulin dynamics to prevent mitosis in cancer cells, leading to cell cycle arrest and, eventually, dose dependent apoptosis.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 21, Issue 5, 1 March 2013, Pages 1248–1256
نویسندگان
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