Discovery of a Highly Tumor-Selective Organometallic Ruthenium(II)–Arene Complex

• Published in: Journal of medicinal chemistry Vol. 57; no. 8; pp. 3546 - 3558
• Main Authors: Clavel, Catherine M, Păunescu, Emilia, Nowak-Sliwinska, Patrycja, Griffioen, Arjan W, Scopelliti, Rosario, Dyson, Paul J
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 24.04.2014; Amer Chemical Soc
• Subjects: Angiogenesis Inhibitors - chemical synthesis; Angiogenesis Inhibitors - pharmacology; Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Chemistry, Medicinal; Chick Embryo; Drug Discovery; HEK293 Cells; Humans; Life Sciences & Biomedicine; Organometallic Compounds - chemical synthesis; Organometallic Compounds - pharmacology; Pharmacology & Pharmacy; Ruthenium Compounds - chemical synthesis; Ruthenium Compounds - pharmacology; Science & Technology; Structure-Activity Relationship; Xenograft Model Antitumor Assays; IN-VITRO; DESIGN; ARENE ANTICANCER COMPLEXES; DRUGS; RUTHENIUM COMPLEXES; REACTIVITY; INHIBITORS; PHASE-I; BINDING; CANCER
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm5002748

A ruthenium(II)–arene complex with a perfluoroalkyl-ligand was found to display remarkable selectivity toward cancer cells. IC50 values on several cancer cell lines are in the range of 25–45 μM, and no cytotoxic effect was observed on nontumorigenic (HEK-293) cells at concentrations up to 500 μM (the maximum concentration tested). Consequently, this complex was used as the basis for the development of a number of related derivatives, which were screened in cancerous and noncancerous cell lines. The lead compound was then evaluated in vivo for antiangiogenic activity in the CAM model and in a xenografted ovarian carcinoma tumor (A2780) grown on the CAM. A 90% reduction in the tumor growth was observed.