title: Design, synthesis and biological evaluation of novel mansonone E derivatives prepared via CuAAC click chemistry as topoisomerase II inhibitors.
abstract: 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.
authors: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.
authors: Zhi-Hong
authors: ZH
authors: Huang
authors: Shi-Tian
authors: ST
authors: Zhuo
authors: Chun-Yan
authors: CY
authors: Li
authors: Hua-Ting
authors: HT
authors: Xie
authors: Ding
authors: D
authors: Li
authors: Jia-Heng
authors: JH
authors: Tan
authors: Tian-Miao
authors: TM
authors: Ou
authors: Zhi-Shu
authors: ZS
authors: Huang
authors: Lian-Quan
authors: LQ
authors: Gu
authors: Shi-Liang
authors: SL
authors: Huang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001665:Binding Sites; D045744:Cell Line, Tumor; D057930:Click Chemistry; D004789:Enzyme Activation / Q000187:drug effects; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D062105:Molecular Docking Simulation; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D009285:Naphthoquinones; D012717:Sesquiterpenes; D059005:Topoisomerase II Inhibitors; C496164:mansonone E
keywords: 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