Cuenca Francisco, Moore Michael J B, Johnson Karin, Guyen Bérangère, De Cian Anne, Neidle Stephen
CRUK Biomolecular Structure Group, The School of Pharmacy, University of London, 29/39 Brunswick Square, London, UK.
Bioorg Med Chem Lett. 2009 Sep 1;19(17):5109-13. doi: 10.1016/j.bmcl.2009.07.033. Epub 2009 Jul 10.
A series of 4,5-di-substituted acridones have been designed and synthesized. Several compounds show high affinity for telomeric G-quadruplex DNA in classical and competition FRET assays, together with low duplex DNA affinity, although they do not show activity in a telomerase assay or evidence of telomere shortening. They have low toxicity against a panel of cancer cell lines and a normal human fibroblast line, and produce potent senescence-based long-term growth arrest in the MCF7 and A549 cancer cell lines.
设计并合成了一系列4,5-二取代吖啶酮。在经典和竞争荧光共振能量转移（FRET）分析中，几种化合物对端粒G-四链体DNA表现出高亲和力，同时对双链DNA亲和力较低，尽管它们在端粒酶分析中未显示活性，也没有端粒缩短的证据。它们对一组癌细胞系和正常人类成纤维细胞系具有低毒性，并在MCF7和A549癌细胞系中产生基于衰老的有效长期生长停滞。
