A new scaffold of topoisomerase I inhibitors: Design, synthesis and biological evaluation

The synthesis of a new hexacyclic system was realized starting from tryptamines and exploiting as a key step a sequential Pd-catalyzed N-arylation/acylation reaction. Having topoisomerases as biological target and the campthotecins class as benchmark, the new scaffold was decorated with substituents having different polarity and tested as Topoisomerase I inhibitors. [Display omitted] •Design and synthesis of a new scaffold of Topo I inhibitors.•The sequential Pd-catalyzed N-arylation/acylation reaction was the key step for the synthesis.•The compounds were evaluated for the antiproliferative activity against three cancer cell lines H-460, HeLa and MSTO-211H.•Compound 13 exhibited the most potent inhibitory activity.•Computational binding mode analysis has been performed on the most active compounds.