桦木醇新型炔基衍生物的合成、结构和细胞毒性活性。
Synthesis, structure and cytotoxic activity of new acetylenic derivatives of betulin.
机构信息
Department of Organic Chemistry, Medical University of Silesia, 4 Jagiellonska Str., 41-200 Sosnowiec, Poland.
出版信息
Molecules. 2013 Apr 17;18(4):4526-43. doi: 10.3390/molecules18044526.
A new series of betulin derivatives containing one or two pharmacophores bearing an acetylenic and carbonyl function at the C-3 and/or C-28 positions has been synthesized and characterized by ¹H- and ¹³C-NMR, IR, MS and elemental analyses. The crystal structure of 28-O-propynoylbetulin was determined by X-ray structural analysis. All new compounds, as well as betulin, were tested in vitro for their antiproliferative activity against human SW707 colorectal, CCRF/CEM leukemia, T47D breast cancer, and against murine P388 leukemia and Balb3T3 normal fibroblasts cell lines. Most of the compounds showed better cytotoxicity than betulin and cisplatin used as reference agent. 28-O-Propynoylbetulin was the most potent derivative, being over 500 times more potent than betulin and about 100 times more cytotoxic than cisplatin against the human leukemia (CCRF/CEM) cell line, with an ID₅₀ value of 0.02 μg/mL.
已经合成了一系列新的桦木醇衍生物，这些衍生物在 C-3 和/或 C-28 位含有一个或两个含有炔基和羰基功能的药效团，并通过 ¹H-NMR、¹³C-NMR、IR、MS 和元素分析进行了表征。通过 X 射线结构分析确定了 28-O-丙炔酰基桦木醇的晶体结构。所有新化合物以及桦木醇均在体外对人 SW707 结直肠、CCRF/CEM 白血病、T47D 乳腺癌以及小鼠 P388 白血病和 Balb3T3 正常成纤维细胞系的抗增殖活性进行了测试。大多数化合物的细胞毒性比桦木醇和用作参考剂的顺铂更强。28-O-丙炔酰基桦木醇是最有效的衍生物，对人白血病（CCRF/CEM）细胞系的活性比桦木醇强 500 多倍，比顺铂强约 100 倍，ID₅₀ 值为 0.02μg/mL。
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