A biflavonoid from Luxemburgia nobilis as inhibitor of DNA topoisomerases

• Published in: Planta medica Vol. 71; no. 6; p. 561
• Main Authors: Oliveira, Marcia C, de Carvalho, Mario G, Grynberg, Noema F, Brioso, Paulo S
• Format: Journal Article
• Language: English
• Published: Germany 01-06-2005
• Subjects: Animals; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - pharmacology; Antineoplastic Agents, Phytogenic - therapeutic use; Biflavonoids - administration & dosage; Biflavonoids - pharmacology; Biflavonoids - therapeutic use; Cell Line, Tumor - drug effects; Dose-Response Relationship, Drug; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - therapeutic use; Humans; Inhibitory Concentration 50; Mice; Ochnaceae; Phytotherapy; Plant Extracts - administration & dosage; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Topoisomerase I Inhibitors
• ISSN: 0032-0943
• DOI: 10.1055/s-2005-864159

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.