Contacts:
Supervisor(s):
Dr. Tarita Biver, Dr. Alessandro Pratesi
Title of the PhD project:
Beyond platinum compounds: studies on the potential cytotoxic activity of new coinage metal complexes
Abstract of the PhD project:
Platinum complexes are used as drugs since the discovery of cisplatin, which is known to produce DNA damages and cell apoptosis. The limits and drawbacks of the treatments based on platinum let the researchers consider other metal centres. Likewise to the search for enhanced new metal-based compounds, there is also an urgent need to achieve a higher selectivity towards cancer cells with respect to the healthy ones. In this regard, much interest is actually devoted to the investigations on the mode-of-action of the new molecules on non-canonical DNA or RNA structures, i.e. G-quadruplexes, i-motifs, and four-way junctions. The project aims at the synthesis and study of new molecules that could bind different targets with a different mechanism of action compared to classical platinum-based ones. Gold complexes are commonly accounted as thioredoxin reductase inhibitors and binders for other biologically-relevant proteins, but it could be interesting to find gold complexes able to bind also genomic targets, especially non-canonical ones. In this frame, the detailed characterisation of the binding mechanisms considers also the comparison with the Ag(I) complex counterpart. On the other hand, there is still much room for studies on species that are supposed to prefer genomic targets but for which information on the binding to RNAs and non-canonical structures of DNA and RNA like G-quadruplexes, i-motifs and four-way junctions is still missing or incomplete. For this purpose, a comparative study of the effects exerted by the different metal centres and different ligands is crucial to enlighten the metal complexes behaviour towards the selected biomolecules. The metal complexes currently under investigation can be divided into four groups: diphenyl-(anthracen-9-ylmethyl)phosphine-Au-X where X=Cl, Br, I; two Ag(I) and Au(I) N-heterocyclic bis carbenes; Au(III), Pt(II), and Pd(II) square-planar complexes with tetradentate ligands; 1,10-Phenanthroline/Pd(II) complexes bearing arene ligands with N or O coordinating groups.
Publications:
• T. Marzo, D. Cirri, C. Gabbiani, T. Gamberi, F. Magherini, A. Pratesi, A. Guerri, T. Biver, F. Binacchi, M. Stefanini, A. Arcangeli, L. Messori, ACS Med. Chem. Lett., 2017, 8(10), 997–1001. Doi: https://doi.org/10.1021/acsmedchemlett.7b00162. "Auranofin, Et3PAuCl and Et3PAuI are highly cytotoxic on colorectal cancer cells: a chemical and biological study”.
• G. Agonigi, L. Biancalana, M. G. Lupo, M. Montopoli, N. Ferri, S. Zacchini, F. Binacchi, T. Biver, B. Campanella, G. Pampaloni, V. Zanotti, F. Marchetti, Organometallics, 2020, 39(5), 645–657. Doi: https://doi.org/10.1021/acs.organomet.9b00681. “Exploring the Anticancer Potential of Diiron Bis-cyclopentadienyl Complexes with Bridging Hydrocarbyl Ligands: Behavior in Aqueous Media and In Vitro Cytotoxicity”.
• F. Binacchi, F. Guarra, D. Cirri, T. Marzo, A. Pratesi, L. Messori, C. Gabbiani, T. Biver, Molecules, 2020, 25, 5446. Doi: https://doi.org/10.3390/molecules25225446. “On the Different Mode of Action of Au(I)/Ag(I)-NHC Bis-Anthracenyl Complexes Towards Selected Target Biomolecules”.
• D. Cirri, C. Bazzicalupi, U. Ryde, J. Bergmann, F. Binacchi, A. Nocentini, A. Pratesi, P. Gratteri, L. Messori, International Journal of Biological Macromolecules, 2022, 211, 506-513. Doi: https://doi.org/10.1016/j.ijbiomac.2022.05.033 “Computationally enhanced X-ray diffraction analysis of a gold(III) complex interacting with the human telomeric DNA G-quadruplex. Unravelling non-unique ligand positioning”.
Oral communications at conferences:
• F. Binacchi, T. Biver, S. Bonnet, L. Messori, A. Pratesi, BIOMET2021, Pisa (I), April 2021, “Pt(II), Pd(II) and Gold(III) tetradentate aromatic complexes. A different way of interaction with relevant biosubstrates”.
• F. Binacchi, T. Biver, S. Bonnet, L. Messori, A. Pratesi, ISMEC2021, Białystok (PL), June 2021, “Mechanistic studies on the binding of platinum, palladium and gold complexes with tetradentate aromatic ligands to biosubstrates: different features for different metal centres”.
• F. Binacchi, E. Bimbi, N. Busto, B. García, A. Pratesi, T. Biver, ISMEC2022, Valencia (SP), June 2022, “1,10-Phenanthroline/Pd(II) complexes bearing arene ligands with N or O coordinating groups: synthesis and bioactivity tests”. Winner of the grant
• F. Binacchi, C. Elia, M. Stifano, L. Garzella, A. Donati, E. Bimbi, D. Cirri, N. Busto, B. García García, S. Bonnet, A. Pratesi, T. Biver, Chemistry for the future, Pisa (I), July 2022, “Beyond platinum compounds: studies on the potential cytotoxic activity of new coinage metal complexes”
Poster communications at conferences:
• T. Marzo, D. Cirri, C. Gabbiani, A. Guerri, T. Biver, F. Binacchi, M. Stefanini, A. Arcangeli, L. Messori, BIOMET16 - XVI PharmacoBioMetallics, Messina (I), October 2016, “Triethylphosphine gold iodide (I), the iodido analogue of Auranofin: comparative studies of a potential antineoplastic agent”.
• T. Biver, F. Binacchi, M. G. Fabbrini, T. Marzo, A. Pratesi, C. Gabbiani, L. Messori, BIOMET2019, Arezzo (I), February 2019 p. 34. “DNA-binding of a Fluorescent Silver(I) Carbene Complex”.
• F. Binacchi, D. Cirri, M. G. Fabbrini, A. Pratesi, T. Marzo, L. Messori, C. Gabbiani, T. Biver, Chemistry for the future, Pisa (I), July 2019, DNA, “G-quadruplex and BSA binding of Au(I)L2/Ag(I)L2 complexes of a NHC-anthracenyl ligand”.
• T. Biver, F. Guarra, F. Binacchi, A. Pratesi, D. Cirri, M. G. Fabbrini, T. Marzo, C. Gabbiani, L. Messori, ICBIC19 - 19th International Conference on Biological Inorganic Chemistry, Interlaken (CH), August 2019, p. 193. “Au(I)-NHC-Anthracenyl and Ag(I)-NHC-Anthracenyl Complexes Binding to Biosubstrates: Some Recent Results with a Focus on Solution Equilibria”.
• F. Binacchi, M. G. Fabbrini, D. Cirri, A. Pratesi, T. Marzo, L. Messori, C. Gabbiani, T. Biver, BIOMET2020, Ancona (I), February 2020. “Mechanistic aspects of the binding to biosubstrates of Au(I)L2/Ag(I)L2 where L = NHC-anthracenyl ligand”.
• Francesca Binacchi, Cassandra Elia, Tarita Biver, Sylvestre Bonnet, Luigi Messori, Alessandro Pratesi, CFF2021, Pisa (I), Online, 30 June – 2 July 2021, “Pd(II) complexes with tetradentate aromatic ligands: a study of ligand dependent interaction with relevant biosubstrates”.
• F. Binacchi, E. Giorgi, M. Stifano, G. Salvadori, N. Busto, B. García, A. Pratesi, T. Biver, PROTEINE 2022, Pisa (I), May 2022, “Anthracenyl functionalised Ag(I)/Au(I) NHC bis-carbene complexes bind bovine serum albumin and show antiproliferative activity”.
• F. Binacchi, M. Stifano, L. Garzella, A. Donati, D. Cirri, N. Busto, B. García, A. Pratesi, T. Biver, EuroBIC-16, Grenoble (FR), July 2022, “A multi-technique approach for the study of the interactions between 1-anthracenyl-3-butyl functionalized Ag(I)/Au(I) NHC bis-carbenes and selected biosubstrates”.
• F. Binacchi, E. Bimbi, N. Busto, B. García, A. Pratesi, T. Biver, INORG2022, Pisa (I), September 2022, “Synthesis, characterisation and biological evaluation of new Pd(II) complexes as potential anticancer agents”.
• F. Binacchi, A. Pratesi, T. Biver, ANALITICA2022, Milazzo (I), September 2022, “On solution equilibria of Ag(I) – anthracenyl biscarbenes binding to biosubstrates: small structure changes produce different thermodynamics”.
Other achievements:
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