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.
References
1
Oliveira M CC, Carvalho M G, Silva C J, Werle A.
A New biflavonoid and other constituents from Luxembergia nobilis (EICHL).
J Bras Chem Soc.
2002;
13
119-23
2
Grynberg N F, Carvalho M G, Velandia J R, Oliveira M C, Moreira I C, Braz-Filho R, Echevarria A.
DNA topoisomerase inhibitors: biflavonoids from Ouratea species.
Braz J Med Biol Res.
2002;
35
819-22
5
Middleton E J r, Kandaswami C, Theoharides C T.
The effects of plant flavonoids on mammalian cells: Implications for inflammation, heart disease, and cancer.
Pharmacol Rev.
2000;
32
673-751
6
Boege F, Straub T, Kehr A, Boesenberg C, Christiansen K, Andersen A, Jakob F, Köhrle J.
Selected novel flavones inhibit the DNA binding on the DNA religation of eukaryotic topoisomerase I.
J Biol Chem.
1996;
271
2262-70
7
Yamashita Y, Kawada S -Z, Nakano H.
Induction of mammalian topoisomerase II dependent DNA cleavage by nonintercalative flavonoids, genistein and orobol.
Biochem Pharmacol.
1990;
39
737-44
8
Quideau S, Jourdes M, Saucier C, Glories Y, Pardon P, Baudry C.
DNA topoisomerase Inhibitor Acutissimin A and other flavano-ellagitannins in red wine.
Angew Chem Int Ed.
2003;
42
6012-4
9
Chowdhury A R, Sharma S, Mandal S, Goswami A, Mukhopadhyay S.
Luteolin, an emerging anti-cancer flavonoid, poisons eukaryotic DNA topoisomerase I.
Biochem J.
2002;
366
653-61
10
Pommier Y, Covey J M, Kerrigan D, Markovits J, Pham R.
DNA unwinding and inhibition of mouse leukemia L1210 DNA topoisomerase I by intercalators.
Nucl Acid Res.
1987;
15
6713-31
12
Mossman T.
Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays.
J Immunol.
1983;
65
55-63
