Design, synthesis and docking study of 5-amino substituted indeno[1,2-c]isoquinolines as novel topoisomerase I inhibitors

5-Amino group-substituted indeno[1,2-c]isoquinolines were designed and synthesized as topoisomerase I inhibitors and a docking model was proposed. Various 5-amino group-substituted indeno[1,2-c]isoquinolines 7a–f were synthesized based on the previous QSAR study as rigid structures of 3-arylisoquinolines. Amino group-substituted compounds, especially 5-piperazinyl indeno[1,2-c]isoquinoline 7f, displayed potent topoisomerase I inhibitory activity as well as cytotoxicities against five different tumor cell lines. A Surflex-Dock docking model of 7f was also studied.