PMID: 11606133Oct 19, 2001Paper

Influence of polyamine architecture on the transport and topoisomerase II inhibitory properties of polyamine DNA-intercalator conjugates

Journal of Medicinal Chemistry
L WangOtto Phanstiel

Abstract

An efficient five-step synthetic method was developed to access a series of spermine derivatives containing appended acridine, anthracene, and 7-chloroquinoline motifs. The derivatives were composed of a spermine fragment covalently tethered at its N4 and N9 positions to an aromatic nucleus via an aliphatic chain (e.g., 8: acridine -[C4 aliphatic tether]-spermine-[C4 aliphatic tether]-acridine). The distance separating the spermine and aromatic nuclei was altered via different tethers composed of four or five methylene units. These bis ligands (8, 9, 12, and 13) were shown to inhibit human DNA topoisomerase II (topo II) activity at 5 microM. Enzymatic activity was assessed as the ability to unknot (decatenate) and cleave kinetoplast DNA (kDNA). Polyamine conjugation did not disrupt the ability of the acridine-spermine conjugates 8 and 9 to inhibit topo II activity as compared with the 9-aminoacridine and 9-(N-butyl)aminoacridine controls (at 5 microM). The parent polyamines, spermine (5 microM) and spermidine (10 microM), had little effect on topo II activity. In general, the bis-substituted spermine derivatives (8, 9, 12, and 13) were more efficient topo II inhibitors at 5 microM than their monosubstituted spermidine counterpa...Continue Reading

References

Sep 1, 1977·Journal of Medicinal Chemistry·A H El MasryW B Pratt
Nov 13, 1992·Journal of Medicinal Chemistry·P A StarkM M Abdel-Monem
Nov 25, 1989·Nucleic Acids Research·M T MullerJ R Spitzner
Jan 1, 1981·Differentiation; Research in Biological Diversity·O Heby
Jan 1, 1984·Annual Review of Biochemistry·C W Tabor, H Tabor
Aug 12, 1983·Science·N VolkowJ D Brodie
Jun 1, 1995·Bioorganic & Medicinal Chemistry·A RodgerI S Haworth
Aug 1, 1996·The International Journal of Biochemistry & Cell Biology·N SeilerJ P Moulinoux

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Citations

Dec 4, 2009·Amino Acids·Andrew J Palmer, Heather M Wallace
Mar 10, 2004·Bioorganic & Medicinal Chemistry Letters·Maria V PapadopoulouWilliam D Bloomer
Jul 20, 2002·European Journal of Medicinal Chemistry·Miguel F BrañaTeresa Barlozzari
Apr 28, 2007·Nature Reviews. Drug Discovery·Robert A Casero, Laurence J Marton
Sep 25, 2009·Investigational New Drugs·Anna KruczynskiNicolas Guilbaud
Feb 26, 2011·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Lianhe YangChaojie Wang
Jul 5, 2005·Bioorganic & Medicinal Chemistry·Ji-Yan PangZhi-Hong Jiang
Jan 11, 2014·Journal of Medicinal Chemistry·Aaron MuthOtto Phanstiel
May 21, 2010·Molecular BioSystems·Brenno A D NetoJaïrton Dupont
Mar 25, 2011·Organic & Biomolecular Chemistry·Tim PhillipsJim A Thomas
Feb 6, 2009·The Journal of Physical Chemistry. B·Michael R DuffChalla V Kumar

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