Development of ruthenium antitumor drugs that overcome multidrug resistance mechanisms

Détails

ID Serval
serval:BIB_70D398232600
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Development of ruthenium antitumor drugs that overcome multidrug resistance mechanisms
Périodique
Journal of Medicinal Chemistry
Auteur(s)
Vock  C. A., Ang  W. H., Scolaro  C., Phillips  A. D., Lagopoulos  L., Juillerat-Jeanneret  L., Sava  G., Scopelliti  R., Dyson  P. J.
ISSN
0022-2623 (Print)
Statut éditorial
Publié
Date de publication
2007
Volume
50
Numéro
9
Pages
2166-2175
Notes
PT - Journal Article PT - Research Support, Non-U.S. Gov't
Résumé
Organometallic ruthenium(II) complexes of the general formula [Ru(eta6-p-cymene)Cl2(L)] and [Ru(eta6-p-cymene)Cl(L)2][BPh4] with modified phenoxazine- and anthracene-based multidrug resistance (MDR) modulator ligands (L) have been synthesized, spectroscopically characterized, and evaluated in vitro for their cytotoxic and MDR reverting properties in comparison with the free ligands. For an anthracene-based ligand, coordination to a ruthenium(II) arene fragment led to significant improvement of cytotoxicity as well as Pgp inhibition activity. A similar, but weaker effect was also observed when using a benzimidazole-phenoxazine derivative as Pgp inhibitor. The most active compound in terms of both Pgp inhibition and cytotoxicity is [Ru(eta6-p-cymene)Cl2(L)], where L is an anthracene-based ligand. Studies show that it induces cell death via inhibition of DNA synthesis. Moreover, because the complex is fluorescent, its uptake in cells was studied, and relative to the free anthracene-based ligand, uptake of the complex is accelerated and accumulation of the complex in the cell nucleus is observed
Mots-clé
Animals/Anthracenes/chemical synthesis/chemistry/pharmacology/Antineoplastic Agents/Cell Line,Tumor/Cell Nucleus/metabolism/Chelating Agents/Crystallography,X-Ray/Drug Resistance,Multiple/Drug Resistance,Neoplasm/Drug Screening Assays,Antitumor/Humans/Ligands/Mice/Molecular Structure/Monoterpenes/Organometallic Compounds/Oxazines/Ruthenium
Pubmed
Web of science
Création de la notice
29/01/2008 18:36
Dernière modification de la notice
20/08/2019 14:29
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