Synthesis and anti-leukaemic activity of pyrrolo[3,2,1-hi]indole-1,2- diones, pyrrolo[3,2,1-ij]quinoline-1,2-diones and other polycyclic isatin derivatives

摘要

To further expand the structure-cytotoxic activity relationships of isatin derivatives and to reduce flexibility in substituent groups at nitrogen, 20 analogues incorporating a ring system between the N1 and C7 atoms of isatin were prepared using a variety of synthetic strategies. This yielded pyrroloindole-, pyrroloquinoline-, pyrroloacridine-, pyrrolophenanthridine- and benzopyrrolophenanthridine-based systems with embedded isatin moieties, the latter possessing a novel carbon skeleton. These compounds were subsequently assessed for their in vitro cytotoxicity against human U937 lymphoma cells, with the brominated pyrroloacridine dione 27 showing the most promising activity (IC _(50) 3.01 μM) after 24 h.