Department of Chemistry, Analytical and Biological Chemistry Research Facility, University College Cork, Western Road, Cork, Ireland.
Org Biomol Chem. 2012 Oct 21;10(39):7912-21. doi: 10.1039/c2ob26181b.
Synthesis of novel 7-substituted isoellipticines and isoellipticinium salts is described, with optimisation of routes, representing a new class of anti-cancer agent. Initial assessment of biological activity using a topoisomerase II decatenation assay and NCI screening highlighted strong anti-cancer activity, further developed in a panel of isoellipticinium salts. Interestingly, low correlation between results of the topoisomerase II decatenation assay and NCI screen throughout the panel suggest that topo II is not the most important biological target with respect to anti-cancer activity in this new class of compounds. Results also suggest that solubility is not the limiting factor in activity of the isoellipticinium salts. Overall, 20 novel ellipticine analogues were prepared and full anti-cancer profiling was completed for 13 isoellipticine derivatives and salts. Two compounds display significant specificity towards CNS cancer cell lines and are lead compounds for future development.
新型 7-取代异长春花碱及其异长春花碱盐的合成为描述对象，优化路线，代表一类新的抗癌药物。使用拓扑异构酶 II 解链试验和 NCI 筛选对生物活性的初步评估突出了很强的抗癌活性，并在一系列异长春花碱盐中得到了进一步开发。有趣的是，在整个异长春花碱盐组中，拓扑异构酶 II 解链试验和 NCI 筛选的结果之间相关性较低，这表明拓扑异构酶 II 不是该类新化合物抗癌活性的最重要生物学靶标。结果还表明，在异长春花碱盐的活性中，溶解度不是限制因素。总体而言，制备了 20 种新型长春花碱类似物，并对 13 种异长春花碱衍生物和盐进行了全面抗癌特性分析。两种化合物对 CNS 癌细胞系具有显著的特异性，是未来开发的先导化合物。
