A biflavonoid from Luxemburgia nobilis as inhibitor of DNA topoisomerases.
The biflavonoid 2'',3''-diidroochnaflavone ( 1), isolated from the leaves of Luxemburgia nobilis, was cytotoxic to murine Ehrlich carcinoma (IC50 = 17.2 microM) and human leukemia K562 cells (IC50 = 89.0 microM) in a concentration-dependent manner in 45 h cell culture. The acetyl (1a) and methyl (1b) derivatives of 1 were not cytotoxic to these tumour cells at 67.0 and 82.0 microM concentrations, respectively. Biflavonoid 1 as well 1a inhibit the activity of human DNA topoisomerases I and II-alpha as observed in relaxation and decatenation assays. In addition, we show that 1 is a DNA interacting agent, which causes DNA unwinding in an assay with topoisomerase I. Also, spectrophotometric titration of 1 with DNA resulted in a pronounced hypochromic effect.
Oliveira
Marcia C
MC
Departamento de Química, Instituto de Ciências Exatas, Universidade Federal Rural do Rio de Janeiro, Seropédica, RJ, Brazil. mccdeo@ibest.com.br
de Carvalho
Mario G
MG
Grynberg
Noema F
NF
Brioso
Paulo S
PS
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D044946:Biflavonoids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D043842:Ochnaceae; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D059004:Topoisomerase I Inhibitors
D000972:Antineoplastic Agents, Phytogenic; D044946:Biflavonoids; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D059004:Topoisomerase I Inhibitors