Structural Modification of 3-arylisoquinolines to Isoindolo[2,1-b]isoquinolinones for the Development of Novel Topoisomerase 1 Inhibitors with Molecular Docking Study

Isoindolo[2,1-b]isoquinolinones 9a-i were designed and synthesized as constrained forms of 3-arylisoquinolines through an intramolecular cyclization reaction. Among the synthesized compounds, 9d exhibited potent topoisomerase 1 inhibitory activity with cytotoxicities against three different tumor cell lines. A Surflex-dock docking study was performed to clarify the topoisomerase 1 inhibitory activity of 9d.



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