Jump to main content
Jump to site search

Issue 37, 2012
Previous Article Next Article

CXCR4 chemokine receptor antagonists: nickel(II) complexes of configurationally restricted macrocycles

Author affiliations

Abstract

Tetraazamacrocyclic complexes of transition metals provide useful units for incorporating multiple coordination interactions into a single protein binding molecule. They can be designed with available sites for protein interactions via donor atom-containing amino acid side chains or labile ligands, such as H2O, allowing facile exchange. Three configurationally restricted nickel(II) cyclam complexes with either one or two macrocyclic rings were synthesised and their ability to abrogate the CXCR4 chemokine receptor signalling process was assessed (IC50 = 8320, 194 and 14 nM). Analogues were characterised crystallographically to determine the geometric parameters of the acetate binding as a model for aspartate. The most active nickel(II) compound was tested in several anti-HIV assays against representative viral strains showing highly potent EC50 values down to 13 nM against CXCR4 using viruses, with no observed cytotoxicity (CC50 > 125 μM).

Graphical abstract: CXCR4 chemokine receptor antagonists: nickel(ii) complexes of configurationally restricted macrocycles

Back to tab navigation

Supplementary files

Publication details

The article was received on 25 May 2012, accepted on 11 Jul 2012 and first published on 16 Jul 2012


Article type: Paper
DOI: 10.1039/C2DT31137B
Citation: Dalton Trans., 2012,41, 11369-11377
  • Open access:
  •   Request permissions

    CXCR4 chemokine receptor antagonists: nickel(II) complexes of configurationally restricted macrocycles

    R. Smith, D. Huskens, D. Daelemans, R. E. Mewis, C. D. Garcia, A. N. Cain, T. N. C. Freeman, C. Pannecouque, E. D. Clercq, D. Schols, T. J. Hubin and S. J. Archibald, Dalton Trans., 2012, 41, 11369
    DOI: 10.1039/C2DT31137B

Search articles by author

Spotlight

Advertisements