Synthesis, cytotoxicity and DNA binding of oxoazabenzo[de]anthracenes derivatives in colon cancer Caco-2 cells

•Copper mediated cyclisation of 1,8-dihydroxyanthraquinone.•Substrates include a series of aminoalcohols and n-alkyl aliphatic heterocycles.•Piperidino derivative displayed comparable cytotoxicity to doxorubicin upon 72 h incubation.•Indirect inhibition of topoisomerase enzymes.

New oxoazabenzo[de]anthracenes derivatives were synthesised and characterised. Their interactions with calf thymus DNA were studied by UV spectrophotometric analysis and a competitive ethidium bromide displacement assay. Cytotoxicity was determined by MTT assay, against colon adenocarcinoma (Caco-2 cells). Among all the oxoazabenzo[de]anthracenes derivatives reported herein only the piperidino derivative exhibited strong DNA binding properties and cytotoxic activity with IC50 values in the range of 16 ± 1.5 μM (72-h treatment). In addition, the piperidino derivative did not directly inhibit topoisomerase I and topoisomerase II enzymes. The results confirm that the presence of the oxoazabenzo[de]anthracenes together with the piperidino functionality is crucial in exerting DNA binding and cytotoxic properties, hence demonstrating promise as a chemical scaffold for further development of new anticancer agents.

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