Tetrasubstituted naphthalene diimide ligands with selectivity for telomeric G-quadruplexes and cancer cells.

Hampel, Sonja M; Sidibe, Assitan; Gunaratnam, Mekala; Riou, Jean-François; Neidle, Stephen

Hampel, Sonja M; Sidibe, Assitan; Gunaratnam, Mekala; Riou, Jean-François; Neidle, Stephen.

Afiliación

Hampel SM; CRUK Biomolecular Structure Group, The School of Pharmacy, University of London, London WC1N 1AX, UK.

Bioorg Med Chem Lett ; 20(22): 6459-63, 2010 Nov 15.

Article en En | MEDLINE | ID: mdl-20932753

RESUMEN

A series of tetrasubstituted naphthalene diimide compounds with N-methylpiperazine end groups has been synthesized and evaluated as G-quadruplex ligands. They have high affinity and selectivity for telomeric G-quadruplex DNA over duplex DNA. CD studies show that they induce formation of a parallel G-quadruplex topology. They inhibit the binding of hPOT1 and topoisomerase IIIα to telomeric DNA and inhibit telomerase activity in MCF7 cells. The compounds have potent activity in a panel of cancer cell lines, with typical IC(50) values of â¼0.1 µM, and up to 100-fold lower toxicity in a normal human fibroblast cell line.

Asunto(s)

G-Cuádruplex; Imidas/química; Imidas/farmacología; Naftalenos/química; Naftalenos/farmacología; Telómero; Línea Celular Tumoral; Dicroismo Circular; Humanos; Ligandos; Modelos Moleculares

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Telómero / G-Cuádruplex / Imidas / Naftalenos Límite: Humans Idioma: En Revista: Bioorg Med Chem Lett Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2010 Tipo del documento: Article Pais de publicación: Reino Unido

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