Guyen Berangere, Schultes Christoph M, Hazel Pascale, Mann John, Neidle Stephen
The School of Chemistry, Queen's University Belfast, Belfast, UK BT9 5AG.
Org Biomol Chem. 2004 Apr 7;2(7):981-8. doi: 10.1039/b316055f. Epub 2004 Mar 10.
We report here the synthesis and evaluation for telomerase-inhibitory and quadruplex DNA binding properties of several rationally-designed quindoline analogues, substituted at the 2- and 7- positions. The ability of these compounds to interact with and stabilise an intramolecular G-quadruplex DNA against increases in temperature was evaluated by a fluorescence-based (FRET) melting assay. The resulting T(m) values were found to correlate with their potency for telomerase inhibition, as measured in an in vitro telomerase TRAP assay. The interactions of a number of compounds with a quadruplex DNA molecular structure were simulated by molecular modelling methods. It is concluded that this class of compound represents a new chemical type suitable for further development as telomerase inhibitors.
我们在此报告了几种在2位和7位进行取代的合理设计的喹吲哚类似物的合成及其对端粒酶抑制和四链体DNA结合特性的评估。通过基于荧光的（FRET）熔解实验评估了这些化合物与分子内G-四链体DNA相互作用并使其免受温度升高影响而稳定的能力。在体外端粒酶TRAP实验中测得的结果表明，所得的熔解温度（Tm）值与其端粒酶抑制效力相关。通过分子建模方法模拟了多种化合物与四链体DNA分子结构的相互作用。得出的结论是，这类化合物代表了一种适合作为端粒酶抑制剂进一步开发的新型化学类型。
