Synthesis, cytotoxicity, and DNA topoisomerase II inhibitory activity of benzofuroquinolinediones.
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.
Rhee
Hee-Kyung
HK
School of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea.
Park
Hyen Joo
HJ
Lee
Sang Kook
SK
Lee
Chong-Ock
CO
Choo
Hea-Young Park
HY
D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors
D015363:Quinolones; D059005:Topoisomerase II Inhibitors; D004317:Doxorubicin