Zong Guanghui, Hirsch Melissa, Mondrik Collin, Hu Zhijian, Shi Wei Q
Department of Chemistry and Biochemistry, J. William Fulbright College of Arts & Science, University of Arkansas, Fayetteville, AR 72701, USA.
Department of Chemistry and Biochemistry, J. William Fulbright College of Arts & Science, University of Arkansas, Fayetteville, AR 72701, USA.
Bioorg Med Chem Lett. 2017 Jun 15;27(12):2752-2756. doi: 10.1016/j.bmcl.2017.04.065. Epub 2017 Apr 21.
Ipomoeassin F is a plant-derived macrocyclic glycolipid with single-digit nanomolar IC values against cancer cell growth. In previous structure-activity relationship studies, we have demonstrated that certain modifications around the fucoside moiety did not cause significant cytotoxicity loss. To further elucidate the effect of the fucoside moiety on the biological activity, we describe here the design and synthesis of several fucose-truncated monosaccharide analogues of ipomoeassin F. Subsequent biological evaluation strongly suggests that the 6-membered ring of the fucoside moiety is essential to the overall conformation of the molecule, thereby influencing bioactivity.
甘薯苦素F是一种植物来源的大环糖脂，对癌细胞生长的半数抑制浓度值在个位数纳摩尔级别。在之前的构效关系研究中，我们已经证明岩藻糖苷部分周围的某些修饰不会导致显著的细胞毒性损失。为了进一步阐明岩藻糖苷部分对生物活性的影响，我们在此描述了几种甘薯苦素F的岩藻糖截短单糖类似物的设计与合成。随后的生物学评估有力地表明，岩藻糖苷部分的六元环对于分子的整体构象至关重要，从而影响生物活性。
