ABSTRACT
Topoisomerase inhibitors are agents with anticancer activity. 7"-O-Methyl-agathisflavone (I) and amentoflavone (II) are biflavonoids and were isolated from the Brazilian plants Ouratea hexasperma and O. semiserrata, respectively. These biflavonoids and the acetyl derivative of II (IIa) are inhibitors of human DNA topoisomerases I at 200 microM, as demonstrated by the relaxation assay of supercoiled DNA, and only agathisflavone (I) at 200 microM also inhibited DNA topoisomerases II-alpha, as observed by decatenation and relaxation assays. The biflavonoids showed concentration-dependent growth inhibitory activities on Ehrlich carcinoma cells in 45-h culture, assayed by a tetrazolium method, with IC50 = 24 +/- 1.4 microM for I, 26 +/- 1.1 microM for II and 10 +/- 0.7 microM for IIa. These biflavonoids were assayed against human K562 leukemia cells in 45-h culture, but only I showed 42% growth inhibitory activity at 90 microM. Our results suggest that biflavonoids are targets for DNA topoisomerases and their cytotoxicity is dependent on tumor cell type.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Enzyme Inhibitors/pharmacology , Flavonoids/pharmacology , Topoisomerase I Inhibitors , Animals , Antineoplastic Agents, Phytogenic/isolation & purification , Brazil , Carcinoma, Ehrlich Tumor/drug therapy , Carcinoma, Ehrlich Tumor/enzymology , Drug Screening Assays, Antitumor , Electrophoresis, Agar Gel , Enzyme Inhibitors/isolation & purification , Flavonoids/isolation & purification , Humans , K562 Cells/drug effects , Leukemia/enzymologyABSTRACT
Topoisomerase inhibitors are agents with anticancer activity. 7"-O-Methyl-agathisflavone (I) and amentoflavone (II) are biflavonoids and were isolated from the Brazilian plants Ouratea hexasperma and O. semiserrata, respectively. These biflavonoids and the acetyl derivative of II (IIa) are inhibitors of human DNA topoisomerases I at 200 æM, as demonstrated by the relaxation assay of supercoiled DNA, and only agathisflavone (I) at 200 æM also inhibited DNA topoisomerases II-alpha, as observed by decatenation and relaxation assays. The biflavonoids showed concentration-dependent growth inhibitory activities on Ehrlich carcinoma cells in 45-h culture, assayed by a tetrazolium method, with IC50 = 24 ± 1.4 æM for I, 26 ± 1.1 æM for II and 10 ± 0.7 æM for IIa. These biflavonoids were assayed against human K562 leukemia cells in 45-h culture, but only I showed 42 percent growth inhibitory activity at 90 æM. Our results suggest that biflavonoids are targets for DNA topoisomerases and their cytotoxicity is dependent on tumor cell type
