Structure-based design, synthesis and evaluation of novel anthra[1,2-d]imidazole-6,11-dione derivatives as telomerase inhibitors and potential for cancer polypharmacology

A series of anthra[1,2-d]imidazole-6,11-dione derivatives were synthesized and evaluated for telomerase inhibition, hTERT expression and suppression of cancer cell growth in vitro. All of the compounds tested, except for compounds 4, 7, 16, 24, 27 and 28 were selected by the NCI screening system. Among them, compounds 16, 39, and 40 repressed hTERT expression without greatly affecting cell growth, suggesting for the selectivity toward hTERT expression. Taken together, our findings indicated that the analysis of cytotoxicity and telomerase inhibition might provide information applicable for further developing potential telomerase and polypharmacological targeting strategy.

A series of diversely imidazole-fused anthraquinone derivatives were synthesized and evaluated for drug-induced telomerase inhibitory activity by TRAP assay, hTERT expression by SEAP assay, and cytotoxicity by SRB assay.Figure optionsDownload as PowerPoint slideHighlights
► A series of imidazole-fused anthraquinone derivatives were synthesized.
► Six of compounds were selected and tested for their anticancer activities by NCI.
► Compounds 20, 24 and 25 showed potent telomerase inhibition activities by TRAP assay.
► Compounds 16, 39 and 40 repressed hTERT expressions in H1299 cells by SEAP assay.