STOADA

Synthesis of Targeted Organometallic Anticancer Drugs and their mode of Action

 Coordinatore ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE 

 Organization address address: BATIMENT CE 3316 STATION 1
city: LAUSANNE
postcode: 1015

contact info
Titolo: Prof.
Nome: Paul
Cognome: Dyson
Email: send email
Telefono: 41216939854
Fax: 41216939885

 Nazionalità Coordinatore Switzerland [CH]
 Totale costo 189˙163 €
 EC contributo 189˙163 €
 Programma FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
 Code Call FP7-PEOPLE-IIF-2008
 Funding Scheme MC-IIF
 Anno di inizio 2009
 Periodo (anno-mese-giorno) 2009-05-01   -   2010-02-28

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE

 Organization address address: BATIMENT CE 3316 STATION 1
city: LAUSANNE
postcode: 1015

contact info
Titolo: Prof.
Nome: Paul
Cognome: Dyson
Email: send email
Telefono: 41216939854
Fax: 41216939885

CH (LAUSANNE) coordinator 189˙163.27

Mappa

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 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

pta    groups    onto    inhibitors    compounds    spectrometry    chemical    biological    reactions    drugs    plasma    ru    attached    flexible    ruthenium    scaffold    molecules    sites    proteins    protein    mass    biologically    stoada    valuable    isozymes    anticancer    therapeutic    drug    active    cell    arene    binding    cycle    studied    function    effect    action    antimetastasis    curcumin   

 Obiettivo del progetto (Objective)

'The project is designed to study a new class of ruthenium antimetastasis compounds, which provides a flexible scaffold onto which various groups of known biological function can be grafted, in order to identify the mechanism of antimetastasis action and obtain superior compounds. In addition, targets will be identified from these compounds using an innovative bio-analytical method. The generic compound which will be used for the study are based on the general structure, Ru(η6-arene)Cl2(pta), and biologically active groups with known therapeutic function, e.g. that induce cell cycle arrest, will be tethered to the arene ring or attached via the ruthenium centre. Key protein targets will then be identified by laser ablation inductively coupled plasma mass spectrometry (ICP-MS). The influence of the inhibitors will be studied and the effect on drug efficacy explored. Drug binding sites will be identified using a mass spectrometric bottom-up or top-down methods which will be very much useful in directing future drug design.'

Introduzione (Teaser)

An EU-funded initiative is investigating new forms of anticancer compounds and the way in which they affect chemical reactions within in the cell.

Descrizione progetto (Article)

Compounds based on ruthenium (Ru), a metallic element, curcumin and the protein plasma thromboplastin antecedent (pta) were studied by the Stoada project. Curcumin is the bright yellow substance found in the spice tumeric. These compounds can provide a flexible scaffold onto which groups of known biological function can be attached. The functional groups are particular groups of atoms within molecules, which determine the chemical reactions of the molecules.

Biological effects of the compounds include halting the normal cell cycle, the cycle of changes involved in replication during the life span of the cell. The work of the 'Synthesis of targeted organometallic anticancer drugs and their mode of action' (Stoada) consortium can provide valuable information regarding the mechanisms behind anticancer activity and enable new improved treatments to be achieved.

The chemical make up of the compounds is determined using nuclear resonance magnetic (NMR) spectroscopy, elemental analysis and mass spectrometry. Analysis is also carried out using biological analyses based on (6-arene) c12(pta) and biologically active groups with a known therapeutic function.

Tests show the ruthenium-based compounds are modest inhibitors of the physiologically dominant carbonic anhydrase isozymes, a type of enzyme. Enzymes are proteins that act as catalysts, speeding up chemical reactions. Isozymes differ in the sequence of amino acids, the building blocks of proteins, but catalyse the same chemical reactions.

Project partners have studied the effect of the inhibitors on the efficiency of anticancer drugs, and the drugs binding sites are identified using mass spectrometry. The Stoada project has made a valuable contribution to future anticancer drug designs.

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