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2002 | 49 | 1 | 177-183
Article title

New carbocyclic analogues of netropsin: Synthesis and inhibition of topoisomerases.

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A series of carbocyclic analogues of netropsin were synthesized and evaluated for their capacity to inhibit human topoisomerases I and II in vitro. The compounds are oligopeptides containing 1,4-di- and 1,2,5-trisubstituted benzene rings and unsubstituted N-terminal NH2 groups. Compounds 4-7 consist of two netropsin-like units linked by aliphatic (tetra- and hexamethylene) chains. In the topoisomerase I and II assay, the relaxation of pBR322 plasmid was inhibited by compounds 4-7 at 100 μM concentration.
Physical description
  • Department of Organic Chemistry, Medical Academy of Bialystok, A. Mickiewicza 2c, 15-230 Białystok, Poland
  • Department of Medicinal Chemistry and Drug Technology, Medical Academy of Bialystok, A. Mickiewicza 2c, 15-230 Białystok, Poland
  • Department of Medicinal Chemistry and Drug Technology, Medical Academy of Bialystok, A. Mickiewicza 2c, 15-230 Białystok, Poland
  • Department of Organic Chemistry, Medical Academy of Bialystok, A. Mickiewicza 2c, 15-230 Białystok, Poland
  • 1. Kopka, M.L., Yoon, Ch., Goodsell, D., Pjura, P. & Dickerson, R.E. (1985) Binding of an antitumor drug to DNA, netropsin and CGCGAATT Br CGCG. J. Mol. Biol. 183, 553-563.
  • 2. Goodsell, D. & Dickerson, R.E. (1986) Isohelical analysis of DNA groove-binding drugs. J. Med. Chem. 29, 727-733.
  • 3. Beerman, T.A., McHugh, M.M., Sigmund, R., Lown, J.W., Rao, K.E. & Bathini, Y. (1992) Effects of analogs of DNA minor groove binder Hoechst 33258 on topoisomerase II and I mediated activities. Biochim. Biophys. Acta 1131, 53-61.
  • 4. Wang, Z., Zimmer, C., Lown, J.W. & Knippers, R. (1997) Effects of bifunctional netropsin-related minor groove-binding ligands on mammalian type I DNA topoisomerase. Biochem. Pharmacol. 53, 309-316.
  • 5. Chen, A.Y. & Liu, L.F. (1994) DNA topoisomerase: essential enzymes and lethal targets. Annu. Rev. Pharmacol. Toxicol. 34, 191-218.
  • 6. Bartulewicz, D., Bielawski, K., Markowska, A., Zwierz, K., Pućkowska, A. & Różański, A. (1998) Synthetic analogues of netropsin and distamycin - synthesis of a new pyridine and carbocyclic analogues of the pyrrolecarboxamide antitumour antibiotics. Acta Biochim. Polon. 45, 41-57.
  • 7. Pućkowska, A., Bartulewicz, D., Markowska, A. & Różański, A. (1999) Synthesis of a carbocyclic bis-lexitropsin as DNA cleaving agent. Acta Polon. Pharm. 56 (Suppl.), 104-111.
  • 8. Polaczkowa, W. (1954) in Preparatyka organiczna; pp. 589-591, PWN, Warszawa (in Polish).
  • 9. Bailly, C. & Chaires, J.B. (1998) Sequence-specific DNA minor groove binders. Design and synthesis of netropsin and distamycin analogues. Bioconjugate Chem. 9, 513-531.
  • 10. Lown, J.W. (1995) Design and development of sequence selective lexitropsin DNA minor groove binders. Drug Dev. Res. 34, 145-183.
  • 11. Rao, K.E. & Sasisekharan, V. (1990) Synthesis of distamycin and netropsin analogs: Part III. Biologically active analogs of tris( m-benzamido) compound. Indian. J. Chem. 29B, 508-513.
  • 12. Kielkopf, C.L., White, S., Szewczyk, J.W., Turner, J.M., Baird, E.E., Dervan, P.B. & Rees, D.C. (1998) A structural basis for recognition of AT and TA base pairs in the minor groove of B-DNA. Science. 282, 111-115.
  • 13. Wang, W. & Lown, J.W. (1992) Anti-HIV-I activity of linked lexitropsins. J. Med. Chem. 35, 2890-2897.
  • 14. White, S., Baird, E.E. & Dervan, P.B. (1997) Orientation preferences of pyrrole-imidazole polyamides in the minor groove of DNA. J. Am. Chem. Soc. 119, 8756-8765.
  • 15. Coley, H.M., Mongelli, N. & D’Incalci, M. (1993) The effects of a benzoic acid mustard derivative of distamycin A (FCE 24517) and related minor groove-binding distamycin analogues on the activity of major grove-binding alkylating agents. Biochem. Pharmacol. 45, 619-626.
  • 16. Takasugi, M., Guendouz, A., Chassignol, M., Decout, J.L., Lhomme, J., Thoung, N.T. & Helene, C. (1991) Sequence-specific photo-induced cross-linking of the two strands of double-helical DNA by psoralen covalently linked to a triple helix forming oligonuclotide. Proc. Natl. Acad. Sci. U.S.A. 88, 5602-5606.
  • 17. Boitte, N., Pommery, N., Colson, P., Houssier, C., Waring, M.J., Henichart, J.-P. & Bailly, C. (1997) Synthesis, DNA-binding and cytotoxic properties of a bis(netropsin) anthracenedione conjugate. Anti-Cancer Drug Des. 12, 481-501.
  • 18. Khorlin, A.A., Krylov, A.S., Grokhovsky, S.L., Zasedatelev, A.S., Gursky, G.V. & Gottikh, B.P. (1980) A new type of AT-specific ligand constructed of two netropsin-like molecules. FEBS Lett. 118, 311-314.
  • 19. Yan, Y., Liu, M. & Gong, B. (1997) Two-ring DNA minor-groove binders consisting of readily available, disubstituted benzene derivatives. Bioorg. Med. Chem. Lett. 7, 1469-1474.
  • 20. Bartulewicz, D., Markowska, A., Wołczyński, S., Dąbrowska, M. & Różański, A. (2000) Molecular modelling, synthesis and antitumour activity of carbocyclic analogues of netropsin and distamycin -new carriers of alkylating elements. Acta Biochim. Polon. 47, 23-35.
  • 21. Bartulewicz, D., Bielawski, K., Bielawska, A. & Różański, A. (2001) Synthesis, molecular modelling, and antiproliferative and cytotoxic effects of carbocyclic derivatives of distamycin with chlorambucil moiety. Eur. J. Med. Chem. 36, 461-467.
  • 22. Bielawski, K., Bielawska, A., Bartulewicz, D. & Różański, A. (2000) Molecular modelling of the interaction of carbocyclic analogues of netropsin and distamycin with d(CGCGAATTCGCG)2. Acta Biochim. Polon. 47, 855-866.
  • 23. Czarny, A., Boykin, D.W., Wood, A.A., Nunn, C.M., Neidle, S., Zhao, M. & Wilson, W.D. (1995) Analysis of van der Waals and electrostatic contributions in the interactions of minor-groove binding benzimidazoles with DNA. J. Am. Chem. Soc. 117, 4716-4717.
  • 24. Jain, P.T., Fornari, F.A., Randolph, J.K., Orr, M.S. & Gewirz, D.A. (1998) Induction of DNA damage, inhibition of DNA synthesis, and suppression of c-myc expression by the topoisomerase I inhibitor, camptothecin, in MCF-7 human breast tumor cells. Biochem. Pharmacol. 55, 1263-1269.
  • 25. Belani, C.P., Doyle, L.A. & Aisner, J. (1994) Etoposide: Current status and future perspectives in the management of malignant neoplasms. Cancer Chemother. Pharmacol. 34, S118-S126.
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