PEPMIDAS

Gold(III)-based anticancer agents: dithiocarbamato-peptide derivatives as improved intracellular drug transfer and delivery systems supported by transporter proteins

Coordinatore	UNIVERSITA DEGLI STUDI DI PADOVA    more  Organization address address: VIA 8 FEBBRAIO 2 city: PADOVA postcode: 35122 contact info Titolo: Prof. Nome: Dolores Cognome: Fregona Email: send email Telefono: -8275169 Fax: -700500523
Nazionalità Coordinatore	Italy [IT]
Totale costo	45˙000 €
EC contributo	45˙000 €
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-2007-2-2-ERG
Funding Scheme	MC-ERG
Anno di inizio	2008
Periodo (anno-mese-giorno)	2008-01-01   -   2010-12-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	UNIVERSITA DEGLI STUDI DI PADOVA  Organization address address: VIA 8 FEBBRAIO 2 city: PADOVA postcode: 35122 contact info Titolo: Prof. Nome: Dolores Cognome: Fregona Email: send email Telefono: -8275169 Fax: -700500523	IT (PADOVA)	coordinator	0.00

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 Obiettivo del progetto (Objective)

'The ultimate objective of this research work is the preparation and evaluation of novel gold(III)-di/tripeptidedithiocarbamato complexes for combating cancer through their enhanced selective delivery at the tumor target site supported by transporter proteins. Platinum(II) drugs are now established as effective antitumour agents, the archetypal example of these being cisplatin. However, their usefulness is limited by their narrow spectrum of activity (not active enough against several types of cancer), and by both the development of acquired resistance after continuous treatment and toxicity (in particular, nephrotoxicity). Thus, several third-generation metal-based drugs have been prepared and tested. In this contest, gold(III) compounds are emerging as a new class of metal complexes with outstanding cytotoxic properties, and are presently being evaluated as potential antitumor agents. In particular, some gold(III)-dithiocarbamato derivatives were proved to be much more cytotoxic in vitro than cisplatin, and showed encouraging results in terms of both high in vivo effectiveness and lack of nephrotoxicity. This research project is concerned with the synthesis and characterization of new gold(III)-dithiocarbamato derivatives of di/tripeptides as improved peptide-based delivery systems, to be evaluated as antitumor drugs. The rationale behind our proposal is to design gold(III) complexes of the type [AuX2(pdtc)] (X = Cl, Br; pdtc = di/tripeptidedithiocarbamate) which can be able to both maintain the antitumor properties and the lack of nephrotoxicity of the previously reported gold(III) analogues, together with an enhanced bioavailability through the di/tripeptide-mediated cellular internalization promoted by transporter proteins. Thus, the enormous potential impact of this new class of gold(III) chemotherapeutic agents relies in their possible site-specific delivery in localized cancers strongly improving their cellular uptake and minimizing unwanted side-effects.'