Bioorganic & medicinal chemistry

Synthesis, cytotoxicity, and DNA topoisomerase II inhibitory activity of benzofuroquinolinediones.

PMID 17194596


Benzofuroquinolinediones (7c and 7d) were synthesized by base-catalyzed condensation of dichloroquinolinediones with phenolic derivatives. Their dialkylaminoalkoxy derivatives (8i-8p) were prepared by reaction with various dialkylaminoalkyl chlorides. The cytotoxicity of the synthesized compounds was evaluated against eight types of human cancer cell lines, and their topoisomerase II inhibition was assessed. In general, the cytotoxicity of benzofuroquinolinediones (8i-8p) was similar or superior to that of doxorubicin and showed more potent inhibitory activity than naphthofurandiones (8a-8h). Also, most of the compounds exhibited excellent topoisomerase II inhibitory activity at a concentration of 5 microM and two compounds, 8d and 8i, showed IC50 values of 1.19 and 0.68 microM, respectively, and were much more potent than etoposide (IC50=78.4 microM), but similar to doxorubicin (IC50=2.67 microM). However their inhibitory activity on topoisomerase I was lower, and 8d and 8i showed IC50 values of 42.0 and 64.3 microM, respectively.