Novel synthetic 9-benzyloxyacridine analogue as both tyrosine kinase and topoisomerase I inhibitor

Multi-target agents against tyrosine kinases and topoisomerases are potentially useful for the effective treatment of cancers. Discovery of new multi-target scaffolds are important for developing such agents. A series of five novel acridine analogues, LXL 1–5, were synthesized and their antiproliferative activity against HepG-2 cell lines were evaluated, among which the 9-benzyloxyacridine analogue, LXL-5, showed inhibitory activity against tyrosine kinases, VEGFR-2 and Src. The results of UV–visible absorption spectra and fluorescence emission spectra, as well as DNA topoisomerase I inhibition assay, indicated topoisomerase I inhibitory activity. Our study suggested that acridine scaffold, previously shown to have no multi-target kinase and topoisomerase inhibitory activity, might be potentially developed as a multi-target inhibitor of tyrosine kinases and topoisomerase I.

Graphical abstractA series of five novel acridine analogues, LXL 1–5, were synthesized and their antiproliferative activity against HepG-2 cell lines were evaluated, among which compound LXL-5 was considered a lead compound for development as a multi-target inhibitor of tyrosine kinase and topoisomerase I.Figure optionsDownload full-size imageDownload as PowerPoint slide