Tumor Targeting of Arene Ruthenium Compounds with New Modes of Action

• Unité de recherche: COST
• Numéro de projet: C12.0120
• Titre du projet anglais: Tumor Targeting of Arene Ruthenium Compounds with New Modes of Action

Mots-clé (Anglais)

Medicinal chemistry; bioorganometallic chemistry; supramolecular chemistry; anti-cancer drugs.

Programme de recherche (Anglais)

COST-Action CM1105 - Functional metal complexes that bind to biomolecules

Description succincte (Anglais)

This project is concerned with the preparation of new organometallic compounds that exhibit anticancer action through a catalytic mechanism of action involving oxidation of key constituents of cells. The mechanism of this catalytic process will be evaluated under controlled conditions and in vitro to evaluate the effects it has specifically on cancer cells. Delivery of these compounds to cancer cells will also be studied in vitro and in vivo and new delivery vectors that target the tumour environment will also be prepared and characterized and used to transport the new organometallic compounds selectively to tumours. Extensive biological studies of all the new compounds and drug delivery systems will be undertaken in order to evaluate whether they offer genuine potential in the clinic compared to the existing arsenal of anticancer drugs. The main goals of the project include: (1) The synthesis of new compounds that induce apoptosis via a catalytic mechanism. (2) Obtaining a detailed knowledge of the catalytic mechanism from model substrates and in cell culture. (3) The development of new drug delivery vehicles that transport the catalysts to tumour tissue. (4) An understanding of the delivery mechanism from in vitro and in vivo studies. Extensive interactions with other members of the COST Action are anticipated and training opportunities for young scientists will be provided.

Autres indications (Anglais)

Full name of research-institution/enterprise: EPF Lausanne Laboratoire de Chimie Organométallique et Médicinale EPFL ISIC-LCOM-BCH2402

Partenaires et organisations internationales (Anglais)

AT; HR; CZ; DK; FI; FR; DE; EL; HU; IS; IE; IL; IT; NL; PL; RO; PT; RS; SI; ES; SE; CH; TR; UK

Résumé des résultats (Abstract) (Anglais)

This project was concerned with the development of two classes of organometallic anti-cancer compounds based on ruthenium. One set of compounds consist of dimers that potentially exert their cytotoxic effect through a catalytic oxidative mechanism of action. The other set comprises supramolecular organometallic compounds that selectively target tumors. A large and diverse range of compounds from both categories were prepared, fully characterized by spectroscopic methods and evaluated in vitro for selective anticancer action. The catalytic oxidative process of the first series of compounds was evaluated under controlled conditions and correlated to the in vitro activity of the compounds on cancer cells. Delivery of the second series of compounds to cancer cells was established in vitro and in vivo. Extensive biological studies of the most relevant new compounds from both series was undertaken and based on the results obtained, new compounds were designed, prepared and evaluated.

Références bases de données (Anglais)

Swiss Database: COST-DB of the State Secretariat for Education and Research Hallwylstrasse 4 CH-3003 Berne, Switzerland Tel. [phone] Swiss Project-Number: C12.0120