Contacts:
Supervisors:
Prof. Fabio Marchetti
Title:
Cyclopentadienyl diiron compounds as potential anticancer agents
Abstract:
The association of iron to several important biochemical pathways and its bio-compatibility make its complexes suitable candidates for drug development. Besides, dinuclear complexes offer the possibility to exploit cooperative effects between the two metals, especially if they are directly bound, and multisite coordination modes. These properties allow reactivity patterns not commonly observed with mononuclear species.
In this setting, cationic Fe(II)-Fe(II) compounds containing an aminocarbyne or a vinyliminium bridging ligand are promising candidates for anticancer drug development. These complexes are available by gram-scale procedures from the commercial Fe2Cp2(CO)4, via stepwise assembly of isocyanide, methyl and alkyne moieties on the diiron frame. Recent studies have revealed that they are soluble and stable in water and display a significant cytotoxicity in vitro, this activity being modulated by the R and R' substituents.
The main target of this PhD project is to tether molecular fragments with a documented biological activity to these scaffolds, since it has been demonstrated that the incorporation of bioactive fragments (e.g. aspirin, ethacrynic acid, ibuprofen, biotin, glucose) within anticancer metal structures may provide a synergic effect enhancing the cytotoxicity of the resulting compounds.
Journal articles:
• Mono-, Di- and Tetra-iron Complexes with Selenium or Sulphur Functionalized Vinyliminium Ligands: Synthesis, Structural Characterization and Antiproliferative Activity, by G. Agonigi, L. K. Batchelor, E. Ferretti, S. Schoch, M. Bortoluzzi, S. Braccini, F. Chiellini, L. Biancalana, S. Zacchini, G. Pampaloni, B. Sarkar, P. J. Dyson, F. Marchetti, Molecules 2020, 25, 1656 [DOI: 10.3390/molecules25071656].
• Diiron Complexes with a Bridging Functionalized Allylidene Ligand: Synthesis, Structural Aspects, and Cytotoxicity, by S. Schoch, L. K. Batchelor, T. Funaioli, G. Ciancaleoni, S. Zacchini, S. Braccini, F. Chiellini, T. Biver, G. Pampaloni, P. J. Dyson, F. Marchetti, Organometallics 2020, 39, 361−373 [DOI: 10.1021/acs.organomet.9b00813].
• Anticancer Potential of Diiron Vinyliminium Complexes, by D. Rocco, L. K. Batchelor, G. Agonigi, S. Braccini, F. Chiellini, S. Schoch, T. Biver, T. Funaioli, S. Zacchini, L. Biancalana, M. Ruggeri, G. Pampaloni, P. J. Dyson, F. Marchetti, Chem. Eur. J. 2019, 25 (65), 14801-14816 [DOI: 10.1002/chem.201902885].
• α-Diimine Homologues of Cisplatin: Synthesis, Speciation in DMSO/Water and Cytotoxicity, by L. Biancalana, L. K. Batchelor, P. J. Dyson, S. Zacchini, S. Schoch, G. Pampaloni, F. Marchetti, New J. Chem. 2018, 42, 17453-17463 [DOI: 10.1039/c8nj04195d].
• Unusual activation pathways of amines in the reactions with molybdenum pentachloride, by N. Bartalucci, M. Bortoluzzi, F. Marchetti, G. Pampaloni, S. Schoch, S. Zacchini, New J. Chem. 2017, 41, 4329-4340 [DOI: 10.1039/c6nj03992h].
Publications:
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Oral communications at congress:
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Poster communications at congress:
• “Cytotoxicity of a Novel Class of Organo-Diiron Complexes”. S. Schoch, G. Agonigi, L. K. Batchelor, L. Biancalana, T. Biver, S. Braccini, F. Chiellini, P. J. Dyson, T. Funaioli, F. Marchetti, G. Pampaloni, S. Zacchini, 47th National Conference of Inorganic Chemistry, Bari, 9-12 September 2019. Best poster award winner.
• “Robust Organo-Diiron Complexes as Potential Anticancer Agents”. S. Schoch, G. Agonigi, L. K. Batchelor, L. Biancalana, T. Biver, S. Braccini, F. Chiellini, P. J. Dyson, T. Funaioli, F. Marchetti, G. Pampaloni, S. Zacchini, 12th International School of Organometallic Chemistry, Camerino, 31 August-4 September 2019.
• “Exploring the Anticancer Potential of Diiron Vinyliminium Complexes”. S. Schoch, G. Agonigi, L. K. Batchelor, T. Biver, P. J. Dyson, T. Funaioli, F. Marchetti, G. Pampaloni, D. Rocco, M. Ruggeri, S. Zacchini, 23rd Workshop Pharmabiometallics 2019, Arezzo, 22-23 February 2019.
