Design,Synthesis And Biological Evaluations Of Novel 3,6-diamide Xanthone Derivatives

The ligands that target G-quadruplex have been attracting medicinal chemists' extensive attentions for their high efficiency and low toxicity in recent years.A novel series of xanthones with terminal amine substituents at xanthone's C3 and C6 positions were designed and synthesized as potential telomeric G-quadruplex DNA ligands.All the designed compounds in the series bind to telomeric G-quadruplex in a “thread intercalation” manner(the interation combined with ?-? stacking and groove intercalation),which was confirmed in molecular docking and spectrometric studies.Among them,10 c and 10 d showed better binding abilities and specific affinity toward G-quadruplex DNA HTG21 than ctDNA in fluorescence assay.The antiproliferative activity of four screened compounds to three cancer cells were examined by MTT in vitro,and their inhibitory effects were to low micromolar range.Furthermore,the PCR stop assay demonstrated that 10 c and 10 d could inhibit the amplification ability of telomerase effectively.The designed compounds in this work have good biological activities,and they could be a reference for the design of novel and selective antitumor drugs.