A Biflavonoid from Luxemburgia nobilis as inhibitor of DNA Topoisomerases

Abstract

The biflavonoid 2′′,3′′-diidroochnaflavone (1), isolated from the leaves of Luxemburgia nobilis, was cytotoxic to murine Ehrlich carcinoma (IC₅₀ = 17.2 μM) and human leukemia K562 cells (IC₅₀ = 89.0 μM) 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 μM concentrations, respectively. Biflavonoid 1 as well 1a inhibit the activity of human DNA topoisomerases I and II-α 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.

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