Structure-based design, synthesis and biological evaluation of novel anthra[1,2-d]imidazole-6,11-dione homologues as potential antitumor agents

•A series of thio-substituted anthra[1,2-d]imidazole-6,11-diones were synthesized.•Six compounds were selected and tested for their anticancer potency by NCI.•Compounds 3, 14 and 16 repressed hTERT expressions in H1299 cells by SEAP assay.

By using fragment-based design strategies, a series of 2-thio-substituted anthra[1,2-d]imidazole-6,11-diones were synthesized and evaluated for hTERT repressing activities, cell proliferations, and NCI 60-cell panel assay. Compounds 2, 3, 4, 11, 15 and 35 were selected by the NCI and 3, 4, 11 and 15 represent the GI50, TGI and LC50, respectively. Among them, all were moderate selectivity toward leukemia cancer except for 4 exhibited distinctive selectivity of CNS and renal cancer with 7.403 and 6.475. The overall of test compounds exhibited different cytostatic and cytotoxic activities for further developing potential application as anticancer drugs.

Graphical abstractA series of diversely imidazole-fused anthraquinone derivatives were synthesized and evaluated for drug-induced telomerase inhibitory activity by hTERT expression by SEAP assay and cytostatic/cytotoxic activities by the NCI for screening program.Figure optionsDownload full-size imageDownload as PowerPoint slide