Interactions of antitumour triazoloacridinones with DNA

• Autorzy: Koba M. , Konopa J.
• Języki publikacji: EN

Abstrakty

EN

Triazoloacridinones (TA) are a new group of potent antitumor compounds, from which the most active derivative, C-1305, has been selected for extended preclinical trials. This study investigated the mechanism of TA binding to DNA. Initially, for selected six TA derivatives differing in chemical structures as well as cytotoxicity and antitumor activity, the capability of noncovalent DNA binding was analyzed. We showed that all triazoloacridinones studied stabilized the DNA duplex at a low-concentration buffer but not at a salt concentration corresponding to that in cells. DNA viscometric studies suggested that intercalation to DNA did not play a major role in the mechanism of the cytotoxic action of TA. Studies involving cultured cells revealed that triazoloacridinone C-1305 after previous metabolic activation induced the formation of interstrand crosslinks in DNA of some tumor and fibroblast cells in a dose dependent manner. However, the detection of crosslink formation was possible only when the activity of topoisomerase II in cells was lowered. Furthermore, it was impossible to validate the relevance of the ability to crosslink DNA to biological activity of TA derivatives.

Słowa kluczowe

EN

biological activity; metabolic activity; DNA intercalation; structure-activity relationship; antitumour agent; triazoloacridinone

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2007
• Tom: 54
• Numer: 2
• Opis fizyczny: p.297-306,fig.,ref.

Twórcy

autor

Koba M.

• Gdansk University of Technology, G.Narutowicza 11/12, 80-952 Gdansk, Poland

autor

Konopa J.

Bibliografia

• Dackiewicz P, Skladanowski A, Konopa J (1995) 32P-postlabelling analysis of adducts formed by mitoxantrone and amentantrone with DNA and homopolydeoxyribonucleotides after enzymatic activation. Chem Biol Interact 98: 153–166.
• Dziegielewski J, Slusarski B, Konitz A, Skladanowski A, Konopa J (2002) Interaction of imidazoacridinones to DNA and its relevance to cytotoxic and antitumor activity. Biochem Pharmacol 63: 1653–1666.
• Hazlehurst LA, Krapcho AP, Hacker MP (1995) Correlation of DNA reactivity and cytotoxicity of a new class of anticancer agents: azaanthracenediones. Cancer Lett 91: 115–124.
• Isaacs RJ, Harris AL, Hickson ID (1996) Regulation of human topoisomerase IIα gene promoter in confluencearrested cells. J Biol Chem 271: 16741–16747.
• Johnson RK, Zee-Cheng RK, Lee WW, Acton EM, Henry DW, Cheng CC (1979) Experimental antitumor activity of aminoanthraquinones. Cancer Treat Rep 63: 425–439.
• Kapuscinski J, Darzynkiewicz Z (1985) Interactions of antitumor agents ametantrone and mitoxantrone (novatrone) with double-stranded DNA. Biochem Pharmacol 34: 4203–4213.
• Konopa J (1983) Adriamycin and daunomycin induce interstrand DNA cross-links in HeLa S3 cells. Biochem Biophys Res Commun 110: 819–826.
• Kusnierczyk H, Cholody WM, Paradziej-Lukowicz J, Radzikowski C, Konopa J (1994) Experimental antitumor activity and toxicity of the selected triazolo- and imidazoacridinones. Arch Immunol Ther Exp 42: 414–423.
• Lee CS, Gibson NW (1993) DNA interstrand cross-links induced by cyclopropylpyrroloindole antitumor agent Bizelesin are reversible upon exposure to alkali. Biochemistry 32: 9108–9114.
• Lemke K, Poindessous V, Skladanowski A, Larsen AK (2004) The antitumor triazoloacridone C-1305 is a topoisomerase II poison with unusual properties. Mol Pharmacol 66: 1035–1042.
• Lemke K, Wojciechowski M, Laine W, Bailly C, Colson P, Baginski M, Larsen AK, Skladanowski A (2005) Induction of unique structural changes in guanine-rich DNA regions by the triazoloacridinone C-1305, a topoisomerase II inhibitor with antitumor activity. Nucleic Acids Res 33: 6034–6047.
• Mazerska Z, Augustin E, Dziegielewski J, Cholody WM, Konopa J (1996) QSAR of acridines. III. Structure-activity relationship for antitumor imidazoacridinones and intercorrelation between in vivo and in vitro tests. Anti- Cancer Drug Des 11: 73–88.
• Mazerska Z, Zamponi S, Marassi R, Martelli S (1997) Electrochemical oxidation of antitumor imidazoacridinone derivatives and the reference 2–hydroxyacridinone. J Electroanal Chem 427: 71–78.
• Mazerski J, Muchniewicz K (2000) The intercalation of imidazoacridinones into DNA induces conformational changes in their side chain. Acta Biochim Polon 47: 65–78.
• Meunier G, De Montauzon D, Bernadou J, Grassy G, Bonnafous M, Cros S, Meunier B (1988) The biooxidation of cytotoxic ellipticine derivatives: a key to structure-activity relationship studies? Mol Pharmacol 33: 93–102.
• Pawlak K, Matuszkiewicz A, Pawlak JW, Konopa J (1983) The mode of action of cytotoxic and antitumor 1–nitroacridines. I. The 1-nitroacridines do not exert their cytotoxic effects by physicochemical binding with DNA. Chem Biol Interact 43: 131–149.
• Pawlak K, Pawlak JW, Konopa J (1984) Cytotoxic and antitumor activity of 1-nitroacridines as an after effect of their interstrand DNA crosslinking. Cancer Res 44: 4289–4296.
• Reinert KE (1991) DNA-helix bending, stiffening, and elongation on ligand binding; analysis for several DNAdrug systems, general viscometric DNA response and stereochemical implications. J Biomol Struc Dynam 9: 331–352.
• Skehan P, Storeng R, Scudiero D, Monks A, McMahon J, Vistica D, Warren JT, Bokesch H, Kenney S, Boyd MR (1990) New colorimetric cytotoxicity assay for anticancer-drug screening. J Nat Cancer Inst 82: 1107–1112.
• Skladanowski A, Konopa J (1994a) Interstrand DNA crosslinking induced by anthracyclines in tumour cells. Biochem Pharmacol 47: 2269–2278.
• Skladanowski A, Konopa J (1994b) Relevance of interstrand DNA crosslinking induced by anthracyclines for their biological activity. Biochem Pharmacol 47: 2279–2287.
• Skladanowski A, Larsen AK, Konopa J, Lemke K (1999) Inhibition of DNA topoisomerase II by antitumor triazoloacridinones in vitro and in tumor cells. Proc Am Assoc Cancer Res 40: 681.
• Suh D, Chaires JB (1995) Criteria for the mode of binding of DNA binding agents. Bioorg Med Chem 3: 723–728.
• Węsierska-Gądek J, Schloffer D, Gueorguieva M, Uhl M, Skladanowski A (2004) Increased susceptibility of poly(ADP-ribose) polymerase-1 knockout cells to antitumor triazoloacridone C-1305 is associated with permanent G2 cell cycle arrest. Cancer Res 64: 4487–4497.