Design, synthesis and biological evaluation of novel mansonone E derivatives prepared via CuAAC click chemistry as topoisomerase II inhibitors

Two series of novel C-9 chloro- and bromo-substituted mansonone E derivatives with triazole moieties at the C-3 position were prepared by using copper-catalysed azide-alkyne cycloaddition Click Chemistry. These compounds were found as potent inhibitors of Topoisomerase II (Topo II) and Topoisomerase I (Topo I). The Topo II-mediated pBR322 DNA relaxation and cleavage assay showed that the derivatives might act as catalytic inhibitors. Their cytotoxic activities against A549, HL-60, K562 and HeLa cells were evaluated, indicating that these compounds were potent antitumour agents. Their structure activity relationships and molecular docking study revealed that the substituents of the triazole were particularly important for cytotoxicity.

Antitumour; Click chemistry; Cytotoxic activity; HPLC; HRMS; High Performance Liquid Chromatography; High Resolution Mass Spectrometer; ME; MF; MTT; Mansonone E; NMR; Topo; Topoisomerase; mansonone E; mansonone F; methyl thiazolyl tetrazolium; nuclear magnetic resonance; topoisomerase.