Design, synthesis and evaluation of telomerase inhibitory, hTERT repressing, and anti-proliferation activities of symmetrical 1,8-disubstituted amidoanthraquinones

A series of symmetrical disubstituded 1,8-diamidoanthraquinones were synthesized and evaluated for anti-proliferation, telomerase inhibitory by TRAP assay, and hTERT expression by SEAP assay. All of the compounds tested, except for compounds 3a and 3s were selected by the NCI screening system. In addition, compounds 4e and 4k exhibited inhibitory effects on telomerase activity. Taken together, our findings indicated that the analysis of cytotoxicity and telomerase inhibition might provide information applicable for further developing potential telomerase targeting strategy.

Graphical abstractA series of diversely symmetrical disubstituded 1,8-diamidoanthraquinones were synthesized and evaluated for telomerase inhibitory activity by TRAP assay, and hTERT expression by SEAP assay.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► A series of symmetrical 1,8-disubstituted amidoanthraquinones were synthesized. ► Compounds 3a and 3s were selected by NCI screening system. ► Compounds 4e and 4k showed the telomerase inhibitory effect by TRAP assay. ► Compounds 3c and 3j showed the best selectivity toward hTERT repressing.