Wojtkielewicz Agnieszka, Długosz Maciej, Maj Jadwiga, Morzycki Jacek W, Nowakowski Michał, Renkiewicz Joanna, Strnad Miroslav, Swaczynová Jana, Wilczewska Agnieszka Z, Wójcik Jacek
Institute of Chemistry, University of Białystok, al. Pilsudskiego 11/4, 15-443 Bialystok, Poland.
J Med Chem. 2007 Jul 26;50(15):3667-73. doi: 10.1021/jm0613572. Epub 2007 Jul 3.
Saponin OSW-1 (5e-G2; 3 beta,16 beta,17 alpha-trihydroxycholest-5-en-22-one 16-O-{O-[2-O-(4-methoxybenzoyl)-beta-D-xylopyranosyl]-(1-->3)-2-O-acetyl-alpha-arabinopyranoside}) analogues: with modified side chain (5a/d-G2), 22-deoxo-23,24,25,26,27-pentanor- (14), 22-deoxo-23-oxa- (17), glycosylated with various monosaccharides (5e-G4/G6/G8), and OSW-1 structural isomer (10) were obtained. The analogues were synthesized using a previously published method for the synthesis of OSW-1. The structures of analogues were fully confirmed by spectroscopic methods, and the S-chirality at C-22 of the structural isomer was established by conformational analysis combined with the NMR spectrometry. The cytotoxicity of the analogues toward several types of malignant tumor cells was examined and compared with that of OSW-1. The results suggest that modification of the steroidal aglycone may lead to compounds with high cytotoxicity.
皂苷OSW - 1（5e - G2；3β，16β，17α - 三羟基胆甾 - 5 - 烯 - 22 - 酮16 - O - {O - [2 - O - （4 - 甲氧基苯甲酰基） - β - D - 吡喃木糖基] - （1→3） - 2 - O - 乙酰基 - α - 阿拉伯吡喃糖苷}）类似物：具有修饰侧链的（5a/d - G2）、22 - 脱氧 - 23，24，25，26，27 - 五降 - （14）、22 - 脱氧 - 23 - 氧杂 - （17）、用各种单糖糖基化的（5e - G4/G6/G8）以及OSW - 1结构异构体（10）已被获得。这些类似物是使用先前发表的用于合成OSW - 1的方法合成的。类似物的结构通过光谱方法得到充分确认，并且通过构象分析结合核磁共振光谱法确定了结构异构体C - 22处的S - 手性。检测了这些类似物对几种类型恶性肿瘤细胞的细胞毒性，并与OSW - 1的细胞毒性进行了比较。结果表明甾体苷元的修饰可能导致具有高细胞毒性的化合物。
