Jung Mankil, Lee Yongnam, Moon Hyung-In, Jung Youngae, Jung Haein, Oh Miyeon
Department of Chemistry, Yonsei University, Seoul, Republic of Korea.
Eur J Med Chem. 2009 Aug;44(8):3120-9. doi: 10.1016/j.ejmech.2009.03.007. Epub 2009 Mar 21.
The total synthesis and anticancer activity of several novel derivatives based on a dauer effect-inducing glycolipid are presented. A versatile and convergent synthesis was accomplished through stereospecific alpha-glycosylation, which produced di- and tri-rhamnoside daumone derivatives. Most of the synthetic derivatives possessed potent anticancer activity against human cancer cell lines. Daumone and deoxyrhamnose trisaccharides with amide side chains had the most potent anticancer activity among all other known glycolipids, with an effective concentration of 20 nM, which is comparable to that of doxorubicin. Conversely, acyclic and macrocyclic daumone derivatives had drastically decreased anticancer activity. Due to the high lipophilic nature of the novel glycolipid derivatives, we propose that the observed anticancer activity is due to their potential to inhibit cell differentiation and proliferation via interaction with the membranes of cancer cells.
介绍了几种基于诱导滞育效应糖脂的新型衍生物的全合成及其抗癌活性。通过立体特异性α-糖基化完成了一种通用且收敛的合成，得到了二鼠李糖苷和三鼠李糖苷道莫酮衍生物。大多数合成衍生物对人癌细胞系具有强大的抗癌活性。在所有其他已知糖脂中，带有酰胺侧链的道莫酮和脱氧鼠李糖三糖具有最强的抗癌活性，有效浓度为20 nM，与阿霉素相当。相反，无环和大环道莫酮衍生物的抗癌活性急剧下降。由于新型糖脂衍生物具有高亲脂性，我们认为观察到的抗癌活性是由于它们有可能通过与癌细胞膜相互作用来抑制细胞分化和增殖。
