State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China.
Eur J Med Chem. 2010 Apr;45(4):1673-7. doi: 10.1016/j.ejmech.2009.12.032. Epub 2009 Dec 23.
Deoxypodophyllotoxin inhibits tubulin polymerization and induces cell cycle arrest at G2/M, followed by apoptosis. In order to find compounds with superior bioactivity and less toxicity, a series of spin-labeled derivatives of deoxypodophyllotoxin were synthesized by reacting 4'-demethyl-4-deoxypodophyllotoxin (DPPT) with N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyloxycarbonyl) amino acids. The cytotoxic activities against three tumor cell lines (HL-60, RPMI-8226, A-549) in vitro and the antioxidative activities in tissues of Sprague Dawley (SD) rats of target compounds were evaluated, and the results indicated that compounds 11a-h were more potent in terms of cytotoxicities and antioxidative activities than either parent compound DPPT or anticancer drug VP-16.
脱氧鬼臼毒素抑制微管蛋白聚合，并诱导细胞周期停滞在 G2/M 期，随后引发细胞凋亡。为了寻找具有更高生物活性和更低毒性的化合物，通过将 4'-去甲-4-脱氧鬼臼毒素（DPPT）与 N-（1-氧代-2,2,6,6-四甲基-4-哌啶基氧羰基）氨基酸反应，合成了一系列脱氧鬼臼毒素的氮杂环丙烷标记衍生物。对目标化合物进行了体外对三种肿瘤细胞系（HL-60、RPMI-8226、A-549）的细胞毒性活性和对 Sprague Dawley（SD）大鼠组织的抗氧化活性评价，结果表明，化合物 11a-h 在细胞毒性和抗氧化活性方面均优于母体化合物 DPPT 或抗癌药物 VP-16。
