Novel bivalent securinine mimetics as topoisomerase I inhibitors

Wen Hou, Hui Lin, Zhen Ya Wang, Martin G. Banwell, Ting Zeng, Ping Hua Sun, Jing Lin*, Wei Min Chen

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    8 Citations (Scopus)


    A series of novel bivalent securinine mimetics incorporating different linkers between C-15 and C-15′ were synthesized and their topoisomerase I (Topo I) inhibitory activities evaluated. It was thus revealed that mimetic R2 incorporating a rigid m-substituted benzene linker exhibits Topo I inhibitory activity three times that of parent securinine. Comprehensive structure-activity relationship analyses in combination with docking studies were used to rationalize the potent activity of these bivalent mimetics. Mechanistic studies served to confirm the deductions arising from docking studies that the active bivalent mimetics not only inhibited complexation between Topo I and DNA but also stabilized the Topo I-DNA complex itself.

    Original languageEnglish
    Pages (from-to)320-328
    Number of pages9
    Issue number2
    Publication statusPublished - 2017


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