抗肿瘤薯蓣皂苷元衍生物的设计与合成(Ⅰ)
The design and synthesis of diosgenin anti-tumor derivatives(Ⅰ)
作者：傅微微;吴亚克;范举正;
Author：
收稿日期： 年卷（期）页码：2010,25(06):-658-663
期刊名称：华西药学杂志
Journal Name：WEST CHINA JOURNAL OF PHARMACEUTICAL SCIENCES
关键字：薯蓣皂苷元;衍生物;合成;抗肿瘤活性;Bcl-2蛋白;分子对接
Key words：
基金项目：
中文摘要
目的针对抗肿瘤活性,设计、合成薯蓣皂苷元衍生物并研究其体外抗肿瘤活性。方法基于作用机制并运用Autodock进行目标分子辅助设计。以薯蓣皂苷元为原料,与氯乙酸缩合,得中间体(Ⅰ)后,再与杂环(哌啶、吗啉、哌嗪)或取代杂环(哌嗪)反应制得化合物Ⅱ~Ⅵ;以薯蓣皂苷元为原料,将其F环开环得到中间体(Ⅶ)后,再与不同的疏水性脂肪酸、芳香酸或酚缩合,制备了化合物Ⅷ~Ⅺ。采用MTT法对人恶性黑色素瘤细胞A375、人肺腺癌细胞A549、人肝癌细胞HepG-2进行体外抗肿瘤活性试验。结果制备的化合物中,除化合物Ⅶ外,其余10个是新化合物,其结构经1HNMR、13CNMR确证。结论薯蓣皂苷元衍生物的初步体外活性测试均表现出良好的抗肿瘤活性,其中,化合物Ⅳ、Ⅵ的抗肿瘤活性与阳性对照1-(3β-薯蓣皂苷元)-3-苄基咪唑溴盐相当。
参考文献
[1]David YL,Bertrand L,Jean-LB.Role of MAPKs and NF-κκBin diosgenin-induced megakaryocytic differentiation and subse-quent apoptosis in HEL cells[J].Inter J Oncology,2006,28:201-207.
[2]Patrick T,Cecile C,Bertrand L,et al.Structure?function rela-tionship for saponin effects on cell cycle arrest and apoptosis inthe human 1547 osteosarcoma cells:a molecular modelling ap-proach of natural molecules structurally close to diosgenin[J].Bioorgan&Med Chem,2005,13:1141-1149.
[3]Ming JL,Zhao W,Yong J,et al.Diosgenin induces cell cycle ar-rest and apoptosis in human leukemia K562 cells with the disrup-tion of Ca2+homeostasis[J].Cancer Chemother Pharmacol,2005,55:79-90.
[4]Ying W,Chi MC,Jen FC,et al.Dioscin(saponin)-inducedgeneration of reactive oxygen species through mitochondria dys-function:a proteomic-based study[J].J Proteome Res,2007,6(12):4703-4710.
[5]Can HZ,You JZ,Ju Z,et al.Construction of a three-dimensionalpharmacophore for Bcl-2 inhibitors by flexible docking and themultiple copy simultaneous search method[J].Bioorgan&MedChem,2007,15:6407-6417.
[6]Rene S,Martina L,Stefan O,et al.Synthesis of dihydrodiosgeninglycosides as mimetics of bidesmosidic steroidal saponins[J].Eur J Org Chem,2003:4003-4011.
[7]Nisachon C,Ngampong K,Boonsong K.A novel synthetic ap-proach from diosgenin to a 17α-hydroxy orthoester via a regio-and stereo-specific rearrangement of an epoxy ester,syntheticcommunications[J].Synth Commu,2006,34(6):961-983.
[8]张洪彬,羊晓东,卿晨,等.甾体咪唑盐类化的物及其制备方法[P].CN2006 10011025.7,2006.
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