Platinum based-drugs currently used in therapy, i.e. cisplatin and its second and third generation derivatives carboplatin and oxaliplatin, were established to elicit their cytotoxic effect through the formation of bifunctional intra- and interstrand DNA adducts at the guanosine residues. Since the discovery of the potent antiproliferative activity of the platinum triamine complex phenanthriplatin and of its analogues, the mechanism of action of monofunctional platinum compounds as anticancer agents have been deeply investigated.1,2 This class of platinum complexes bearing only one labile ligand is able to form only a single covalent bond at the N7 position of guanine residues without significantly bending or unwinding the double helix but indeed forming lesions of such a shape that result able to elude cellular repair responses and to potentially interact with other-than-DNA targets, thus affording a novel activity profile. Starting from those assumptions and considering the promising results obtained of our research group in the synthesis of aminomethylimidazole based dichloride platinum complexes,3 we synthesised a series of cationic triamine platinum compounds of general formula [Pt(N-N’)N’Cl]X- where N-N’ is an aminomethylimidazole ligand and the N’ an imidazole ring, both bearing the same alkyl group at the N1 position. The resulting platinum complexes were analytically characterized and biologically evaluated on different cancer cell lines known for their aggressive behaviour (triple negative breast cancer)4 and for their poor sensitivity to the common cisplatin chemotherapy. Moreover, several in vitro assays were performed in order to better define their antitumor activity and target selectivity.

In vitro anticancer activity evaluation of new cationic platinum(II) complexes based on imidazole mojety / I. Rimoldi, G. Facchetti, N. Ferri - In: BioMet16 : XVI Workshop on PharmacoBioMetallics[s.l] : CIRCMSB, 2016 Oct 28. - pp. 1-1 (( Intervento presentato al 16. convegno BioMet tenutosi a Messina nel 2016.

In vitro anticancer activity evaluation of new cationic platinum(II) complexes based on imidazole mojety

I. Rimoldi;G. Facchetti;
2016-10-28

Abstract

Platinum based-drugs currently used in therapy, i.e. cisplatin and its second and third generation derivatives carboplatin and oxaliplatin, were established to elicit their cytotoxic effect through the formation of bifunctional intra- and interstrand DNA adducts at the guanosine residues. Since the discovery of the potent antiproliferative activity of the platinum triamine complex phenanthriplatin and of its analogues, the mechanism of action of monofunctional platinum compounds as anticancer agents have been deeply investigated.1,2 This class of platinum complexes bearing only one labile ligand is able to form only a single covalent bond at the N7 position of guanine residues without significantly bending or unwinding the double helix but indeed forming lesions of such a shape that result able to elude cellular repair responses and to potentially interact with other-than-DNA targets, thus affording a novel activity profile. Starting from those assumptions and considering the promising results obtained of our research group in the synthesis of aminomethylimidazole based dichloride platinum complexes,3 we synthesised a series of cationic triamine platinum compounds of general formula [Pt(N-N’)N’Cl]X- where N-N’ is an aminomethylimidazole ligand and the N’ an imidazole ring, both bearing the same alkyl group at the N1 position. The resulting platinum complexes were analytically characterized and biologically evaluated on different cancer cell lines known for their aggressive behaviour (triple negative breast cancer)4 and for their poor sensitivity to the common cisplatin chemotherapy. Moreover, several in vitro assays were performed in order to better define their antitumor activity and target selectivity.
Settore CHIM/03 - Chimica Generale e Inorganica
Settore BIO/14 - Farmacologia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/505351
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