Novel synthetic acridine-based derivatives as topoisomerase I inhibitors

Novel DNA binding agents against topoisomerases are needed for effective treatment of cancers. A series of new acridine-based derivatives 7a–7d were synthesized and their antiproliferative activity against K562 and HepG-2 cell lines were evaluated. Compound 7c with pyridin-2-yl-methanamino group substituted at the C9 position of acridine showed good antitumor activity against both cell lines. The DNA-binding affinity of compound 7c was evaluated by UV–vis absorption spectra and fluorescence emission spectra. DNA topoisomerase I mediated relaxation of plasmid pBR322 DNA was also tested. Our results suggested that compound 7c with good antitumor activity and topoisomerase I inhibition activity can be developed as a prime candidate for further chemical optimization.

Graphical abstractA series of acridine-based analogs 7a–7d were synthesized and tested for their antiproliferative activity against K562 and HepG-2 cancer cell lines, as well as DNA-binding properties. Compound 7c showed good antitumor activity and topoisomerase I inhibition activity, which makes it a good candidate for further chemical optimization.Figure optionsDownload full-size imageDownload as PowerPoint slide