2. Academic Validation
  3. A novel series of G-quadruplex ligands with selectivity for HIF-expressing osteosarcoma and renal cancer cell lines

A novel series of G-quadruplex ligands with selectivity for HIF-expressing osteosarcoma and renal cancer cell lines

  • Bioorg Med Chem Lett. 2012 Sep 15;22(18):5984-8. doi: 10.1016/j.bmcl.2012.07.009.
Caterina M Lombardo 1,  Sarah J Welsh,  Sandra J Strauss,  Aaron G Dale,  Alan K Todd,  Rupesh Nanjunda,  W David Wilson,  Stephen Neidle
Affiliations

Affiliation

  • 1 UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK.
PMID: 22889802 DOI: 10.1016/j.bmcl.2012.07.009
Abstract

A series of naphthalene derivatives with disubstituted triazole side-arms have been assembled by Click Chemistry. Lead compounds show a high level of selectivity for renal, osteo- and Ewing's sarcomas that express the HIF-1α transcription factor. They also interact selectively with the quadruplex DNAs located in the promoter of the HIF genes and it is suggested that the mechanism of action involves inhibition of transcription by drug-mediated quadruplex stabilization in these regions.

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