Design, Synthesis Of Disubstituted Xanthones Targeting Telomeric G-quadruplex DNA And Studies Of The Biological Activities

Now, designing the anti-tumor drug based on G-quadruplex as the target becomes a hot spot of the chemists and biologists. This work has been designed and synthesized a series of xanthone derivatives with double amino group targeting G-quadruplex and the structures have been characterized by means of ESI-MS and NMR. The antitumor activity and the apoptosis of xanthone derivatives were investigated by MTT assay, AO/EB staining and flow cytometry assay. The results show that the xanthone derivatives have good antitumor activity. Futher,circular dichroism(CD), UV-Vis absorption, fluorescence, PCR stop assay and molecular modeling were used to study the interactions and binding affinity between the xanthone derivatives and telomeric G-quadruplex DNA. The results suggest that the xanthone could induce and stabilize the single-stranded telomeric DNA to form G-quadruplex HTG21. These results will provide a new strategy to discover and develop novel antitumor drugs targeting G-quadruplex.