Novel pyrrolo[3,2-f]quinolines: synthesis and antiproliferative activity

Novel pyrrolo[3,2,f]quinoline derivatives have been synthesized and tested as antiproliferative agents. They are characterized by an angular aromatic tricyclic system, to which a methyl group can be bound at position 7, and by a methanesulfon-anisidide side chain as such, or lacking the m-methoxy substituent at position 1. The novel compounds were shown to exhibit cell growth inhibitory properties when tested against the NCI panel of cell lines, in particular those obtained from leukemias. Although the compounds are able to stimulate topoisomerase II poisoning at high concentration, the cell growth inhibition properties do not appear to rest principally on this mechanism of action. Overall, the most active proved to be compound 9, having the m-methoxy substituent typical of amsacrine, followed by the 7-methyl derivative 10 and by the unsubstituted compound 8. Comparison with previously investigated regioisomers shows modulation of activity dictated by the position and conformational freedom of side-chain groups.