Bioorganic & Medicinal Chemistry, 2011, 19(1):295-305.

Synthetic conjugates of genistein affecting proliferation and mitosis of cancer cells

Aleksandra Rusin, Jadwiga Zawisza-Puchałka, Katarzyna Kujawa, et al

Department of Tumor Biology, Maria Sklodowska-Curie Memorial Cancer Center and the Institute of Oncology, Wybrzeze AK 15, 44-100 Gliwice, Poland; et al

This paper describes the synthesis and antiproliferative activity of conjugates of genistein (1) and unsaturated pyranosides. Constructs linking genistein with a sugar moiety through an alkyl chain were obtained in a two-step synthesis: in a first step genistein was converted into an intermediate bearing an ω-hydroxyalkyl substituent, containing two, three or five carbon atoms, at position 7, while the second step involved Ferrier glycosylation reaction, employing glycals. Antiproliferative activity of several genistein derivatives was tested in cancer cell lines in vitro. The most potent derivative, Ram-3 inhibited the cell cycle, interacted with mitotic spindles and caused apoptotic cell death. Neither genistein nor the sugar alone were able to influence the mitotic spindle organization. Our results indicate, that conjugation of genistein with certain sugars may render the interaction of derivatives with new molecular targets.

英国《生物有机与药物化学》，2011年1月

人工合成金雀异黄素共轭物影响癌症细胞的扩散和有丝分裂

亚历山大 卢森，雅德维加 扎维斯赞-普查卡，卡塔齐娜 库加瓦等

波兰纪念玛丽亚 · 居里癌症中心肿瘤研究所肿瘤生物学部等

本文介绍了染料木黄酮 (1) 和不饱和吡喃糖苷复合物的合成及抗增殖活性。通过二步法合成，得到了通过烷基链糖基团与染料木素连接的结构︰ 第一步金雀异黄素被转换了成被ω-羟烷基取代的中间产物，在位置 7含有两个、 三个或五个碳原子，则第二个步骤涉及使用糖醇的费里尔糖基化反应。在体外肿瘤细胞中测试了几种染料木黄酮衍生物的抗增殖活性。最有效的衍生物，Ram-3 抑制了细胞周期，与有丝分裂纺锤波相互作用，并引起细胞凋亡。单独的金雀异黄素或者单糖都不能影响分裂纺锤体组织。我们的结果表明，染料木黄酮与某些糖的复合物可能提供衍生物与新的分子靶点的相互作用。