摘要：In this study,we designed and synthesized a series of phthalazinone acridine derivatives as dual PARP and Topo *** assays indicated that most of the compounds significantly inhibited multiple cancer cells *** addition,all the compounds displayed Topo Ⅱ inhibition activity at 10 mol/L,and also possessed good PARP-1 inhibitory *** mechanistic studies showed that compound 9 a induced remarkable apoptosis and caused prominent S cell cycle arrest in HCT116 *** study suggested that 9 a inhibiting Topo and PARP concurrently can be a potential lead compound for cancer therapy.

摘要：DNA methyl transferase(DNMT) and histone deacetylase(HDAC) are well recognized epigenetic targets for discovery of antitumor *** this study,we designed and synthesized a series of nucleoside base hydroxamic acid derivatives as DNMT and HDAC dual *** assays and enzymatic inhibitory activity tests indicated that compound 204 exhibited potent DNMT1 and HDAC1/6 inhibitory potency simultaneously in enzymatic levels and at cellular levels,inducing hypomethylation of p16 and hyperacetylation of histones H_(3) K9 and H4 ***,204 remarkably inhibited proliferation against cancer cells U937 by prompting G0/G1 cell cycle *** docking models explained the functional mechanism of 204 inhibiting DNMT1 and *** studies on metabolic profiles revealed that 204 showed desirable stability in liver *** study suggested that 204 inhibiting DNMT and HDAC concurrently can be a potential lead compound for epigenetic cancer therapy.