Novel synthetic 9-benzyloxyacridine analogue as both tyrosine kinase and topoisomerase I inhibitor |
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Authors: | Xu-Liang Lang Qin-Sheng Sun Yu-Zong Chen Lu-Lu Li Chun-Yan Tan Hong-Xia Liu Chun-Mei Gao Yu-Yang Jiang |
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Affiliation: | Department of Chemistry,Tsinghua University,Beijing 100084,China b The Ministry-Province Jointly Constructed Base for State Key Lab-Shenzhen Key Laboratory of Chemical Biology,Shenzhen 518055,China c Bioinformatics and Drug Design Group,Department of Pharmacy,Centre for Computational Science and Engineering,117543 Singapore,Singapore d Shenzhen Anti-Tumor Drug Development Engineering Laboratory,The Graduate School at Shenzhen,Tsinghua University,Shenzhen 518055,China e School of Medicine,Tsinghua University,Beijing 100084,China |
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Abstract: | 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. |
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Keywords: | Acridine Topoisomerases Tyrosine kinases Antitumor DNA-binding |
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