CRUK Biomolecular Structure Group, The School of Pharmacy, University of London, London WC1N 1AX, UK.
Bioorg Med Chem Lett. 2010 Nov 15;20(22):6459-63. doi: 10.1016/j.bmcl.2010.09.066. Epub 2010 Sep 17.
A series of tetrasubstituted naphthalene diimide compounds with N-methylpiperazine end groups has been synthesized and evaluated as G-quadruplex ligands. They have high affinity and selectivity for telomeric G-quadruplex DNA over duplex DNA. CD studies show that they induce formation of a parallel G-quadruplex topology. They inhibit the binding of hPOT1 and topoisomerase IIIα to telomeric DNA and inhibit telomerase activity in MCF7 cells. The compounds have potent activity in a panel of cancer cell lines, with typical IC(50) values of ∼0.1 μM, and up to 100-fold lower toxicity in a normal human fibroblast cell line.
已经合成了一系列带有 N-甲基哌嗪端基的四取代萘二酰亚胺化合物，并将其作为 G-四链体配体进行了评估。它们与双链 DNA 相比，对端粒 G-四链体 DNA 具有高亲和力和选择性。CD 研究表明，它们诱导形成平行的 G-四链体拓扑结构。它们抑制 hPOT1 和拓扑异构酶 IIIα 与端粒 DNA 的结合，并抑制 MCF7 细胞中的端粒酶活性。这些化合物在一系列癌细胞系中具有很强的活性，典型的 IC（50）值约为 0.1 μM，在正常人成纤维细胞系中的毒性低 100 倍。
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