二取代邻菲罗啉衍生物的合成及其与启动子和人端粒G-四螺旋DNA的键合研究

Six novel di-substituted phenanthroline derivatives 5a-7a and 3b-5b have been prepared, and their binding interactions with human telomeric (h-telo) and the promoter c-kit2 and c-myc G-quadruplex DNAs were investigated. All the compounds are potent stabilisers of the G-quadruplex structures and the compounds 3b, 4b, and 5b exhibit a high G-quadruplex selectivity over duplex. The binding affinities of these compounds to G-quadruplex are higher than to duplex DNA. CD spectra show that the compound can induce the formation of anti-parallel structure of h-telo G-quadruplex. Each h-telo quadruplex binds two compound molecules by the end-stacking mode. Six new compounds are able to inhibit significantly the telomerase activity at lowμM concentration.