Interactions of the Oxidation Products of Papaverine with Guanine Quadruplexes

• Autorzy: Mądry L. , Gałęzowska E. , Głuszyńska A. , Hermann T. , Zabel M. , Juskowiak B.
• Języki publikacji: EN

Abstrakty

EN

The interactions of G-quadruplex DNA with two oxidation products of papaverine, 6a,12a-diazadibenzo-[a,g]fluorenylium derivative (1) and 2,3,9,10-tetramethoxy-12- oxo-12H-indolo[2,1-a]isoquinolinium cation (2) were investigated. Effect of the organic modifier (EtOH) and NaCl on the spectral properties and aggregation of free ligands and on the DNA-binding affinity were assessed. Ligand 1 exhibited tendency for aggregation and showed higher binding selectivity for G-quadruplex DNA over double-stranded DNA. Both ligands were capable of interacting with DNA according to three binding modes: (i) electrostatic interactions, (ii) classical intercalation to dsDNA, and (iii) the specific binding to quadruplex DNA. The cytotoxic activity of ligand 2 was generally higher than that for ligand 1, approaching a micromolar concentration level that may suggest its telomerase inhibition activity.

Słowa kluczowe

EN

DNA-binding; G-quadruplex DNA; papaverine; telomerase inhibitor

• Wydawca: Polskie Towarzystwo Chemiczne
• Czasopismo: Polish Journal of Chemistry
• Rocznik: 2006
• Tom: Vol. 80, nr 6
• Strony: 921--929
• Opis fizyczny: Bibliogr. 24 poz., rys.

Twórcy

autor

Mądry L.

autor

Gałęzowska E.

autor

Głuszyńska A.

autor

Hermann T.

autor

Zabel M.

autor

Juskowiak B.

• Faculty of Chemistry, A. Mickiewicz University, 60-780 Poznan, Poland

Bibliografia

• 1.  Williamson J.R., Annu. Rev. Biophys. Biomol. Struct., 23, 703 (1994).
• 2.  Davis J.T., Angew. Chem. Int. Ed., 43, 668 (2004).
• 3.  Neidle S. and Parkinson G., Curr. Opin. Struct. Biol., 13, 275 (2003).
• 4.  Neidle S. and Parkinson G., Nat. Rev.. Drug Discovery, l, 383 (2002).
• 5. Sun D., Thompson B., Cathers B.E., Salazar M., Kerwin S.M., Trent J.O., Jenkins T.C., Neidle S. and Hurley L.H., J. Med. Chem., 40, 2113 (1997).
• 6. Arthanari H. and Bolton P.H., Chem. Biol., 8, 221 (2001).
• 7.  Izbicka E., Wheelhouse R.T., Raymond E., Davidson K.K., Lawrence R.A., Sun D., Windle B., Hurley L.H. and Von Hoff D.D., Cancer Res., 59, 639 (1999).
• 8.  Harrison R.J., Gowan S.M., Kelland L.R. and Neidle S., Bioorgan. Med. Chem. Lett., 9, 2463 (1999).
• 9. Fedoroff O.Y., Salazar M., Han H., Chemeris V.V., Kerwin S.M. and Hurley L.H., Biochemistry, 37, 12367(1998).
• 10. Read M.A., Wood A.A., Harrison J.R., Gowan S.M., Kelland L.R., Dosanjh H.S. and Neidle S., J. Med.Chem., 42, 4538 (1999).
• 11. Juskowiak B., Galezowska E., Koczorowska N. and Hermann T.W., Bioorgan. Med. Chem. Lett., 14,3627 (2004).
• 12. Juskowiak B., Galezowska E., Kościelna H., Hermann T.W. and Piotrowska K., PolishJ. Chem., 79,831 (2005).
• 13. Hermann T.W., Girreser U., Michalski P. and Piotrowska K., Arch. Pharm. Pharm. Med. Chem., 335,167(2002).
• 14. Girreser U., Hermann T.W. and Piotrowska K., Arch. Pharm. Pharm. Med. Chem., 336, 401 (2003).
• 15. Scatchard G., Ann. N.Y. Acad. Sci., 51, 660 (1949).
• 16. Skehan P., Storeng R., Scudiero D., Monks A., McMahon J., Vistica D., Warren J.T., Bokesch H.,Kenney S. and Boyd M.R. , J. Nad. Cancer Inst., 82, 1107 (1990).
• 17. Zee-Cheng R.K. and Cheng C.C., J. Med. Chem., 21, 199 (1978).
• 18. Manning G.S., Q. Rev. Biophys., 2, 179 (1978).
• 19. Read M.A. and Neidle S., Biochemistry, 39, 13422 (2000).
• 20. Kern J.T., Thomas P.W. and Kerwin S.M., Biochemistry, 41, 11379 (2002).
• 21. Gavathiotis E., Heald R.A., Stevens M.F.G. and Searle M.S., J. Mol. Biol. , 334, 25 (2003).
• 22. Mergny J.-L., Phan A.-T. and Lacroix L., FEBS Lett., 435, 74 (1998).
• 23. Read M.A., Harrison J.R., Romagnoli B., Tanious F.A., Gowan S.H., Reszka A.P., Wilson D.W., Kelland L.R. and Neidle S., Proc. Natl. Acad. Sci. USA, 98, 4844 (2001).
• 24. Perry P.J., Gowan S.M., Reszka A.R, Polucci R, Jenkins T.C., Kelland L.R. and Neidle S., J. Med. Chem., 41, 3253 (1998).