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 ...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 HepC-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.展开更多
基金supports from the Ministry of Science and Technology of China(Nos. 2012ZX09506001-010,2012AA020305 and 2011DFA30620)the National Natural Science Foundation of China(Nos.21272134 and 20902053)Shenzhen Sci & Tech Bureau(No. JCYJ20120831165730905)
文摘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 HepC-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.
