Stewart Scott G, Ho Louisa A, Polomska Marta E, Percival Alexander T, Yeoh George C T
The School of Biomedical, Biomolecular & Chemical Sciences, The University of Western Australia, Crawley, Crawley, WA 6009 (Australia).
ChemMedChem. 2009 Oct;4(10):1657-67. doi: 10.1002/cmdc.200900238.
We report the syntheses of five natural product maleimide and maleic anhydrides from the mushroom Antrodia camphorata. The ability of these compounds to affect proliferation in non-tumourigenic and tumourigenic liver progenitor cell lines was monitored by the Cellscreen system, a novel and nondestructive rapid-screening instrument. Additionally, a range of new aryl-functionalised differentiated derivatives were prepared through a Suzuki cross-coupling reaction to influence cell-growth effects. Several derivatives radically slowed the proliferation of liver progenitor cells; however, of particular interest were two maleic anhydride derivatives containing aryl tethers. These analogues demonstrated selectivity for limiting the proliferation of tumourigenic progenitor cells in comparison with their non-tumourigenic counterparts. Also highlighted is the application of the Cellscreen system in medicinal chemistry to rapidly measure the effect of compound libraries on cell proliferation.
我们报告了从樟芝中合成五种天然产物马来酰亚胺和马来酸酐。通过Cellscreen系统（一种新型的非破坏性快速筛选仪器）监测了这些化合物对非致瘤性和致瘤性肝祖细胞系增殖的影响。此外，通过铃木交叉偶联反应制备了一系列新的芳基官能化衍生化产物，以影响细胞生长效应。几种衍生物极大地减缓了肝祖细胞的增殖；然而，特别令人感兴趣的是两种含有芳基连接基团的马来酸酐衍生物。与它们的非致瘤性对应物相比，这些类似物显示出限制致瘤性祖细胞增殖的选择性。还强调了Cellscreen系统在药物化学中的应用，以快速测量化合物库对细胞增殖的影响。
