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 b y a methanesulfonanisidide side chain as such, or lacking the m-methoxy sub stituent at position 1. The novel compounds were shown to exhibit cell grow th inhibitory properties when tested against the NCI panel of cell lines, i n particular those obtained from leukemias. Although the compounds are able to stimulate topoisomerase II poisoning at high concentration. the cell gr owth inhibition properties do not appear to rest principally on this mechan ism of action. Overall, the most active proved to be compound 9, having the m-methoxy substituent typical of amsacrine, followed by the 7-methyl deriv ative 10 and by the unsubstituted compound 8. Comparison with previously in vestigated regioisomers shows modulation of activity dictated by the positi on and conformational freedom of sidechain groups. (C) 2001 Elsevier Scienc e Ltd. All rights reserved.