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

2013; Elsevier BV; Volume: 68; Linguagem: Inglês

10.1016/j.ejmech.2013.07.011

1768-3254

Zhihong Huang, Shitian Zhuo, Chunyan Li, Hua-Ting Xie, Ding Li, Jia‐Heng Tan, Tian‐Miao Ou, Zhi‐Shu Huang, Lian‐Quan Gu, Shi‐Liang Huang,

Synthesis and biological activity

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.