Biancalana Lorenzo

biancalana

Contacts: Questo indirizzo email è protetto dagli spambots. E' necessario abilitare JavaScript per vederlo.


Supervisor: Prof Fabio Marchetti


Title: Design, Synthesis and Evaluation of New Transition Metal Complexes as Anticancer Agents


Abstract: Transition metal complexes have been at the forefront of chemotherapy since the discovery of cisplatin's activity back in the 1960s. In the last decades, some classes of ruthenium complexes emerged for their promising cytotoxic and/or anti-metastatic properties. In particular, much work has focused on piano-stool Ru(II) complexes of the type [(η6-arene)RuXYZ]0/+ where X, Y, Z are three coordination positions occupied by bidentate or monodentate ligands. The piano-stool motif offers much scope for molecular design, by varying the nature and the size of the substituents belonging to each ligand.
One of the main problems associated with cisplatin and other metal-based chemotherapeutic agents is their low selectivity, i.e. ability to discriminate between tumoral and healthy cells. In this context, the synthesis of metal complexes containing organic fragments with known biological functions (bioactive molecules) can lead to enhanced anticancer activities, if the target of the bioactive molecule is over-expressed or uniquely expressed in cancer cells.
In this regard, we focused our attention of enzyme inhibitors. Ethacrynic acid (EA) is an inhibitor of Glutathione-S-Transferases (GST), a class of enzymes involved in cellular detoxification. GST enzymes show an increased activity in some types of cancerous cells and this contributes to drug resistance. Ethacrynic acid and its derivatives reduce drug resistance by inhibiting GST enzymes. Hence, the EA skeleton has been successfully incorporated in ruthenium(II) and Platinum(II) complexes with very promising pharmacological results in vitro.
My PhD project is aimed to the synthesis, characterization and evaluation of the anticancer activity of new transition metal complexes functionalized with small bioactive molecules. The ligands will be prepared by coupling Ethacrynic acid or other enzyme inhibitors, respectively, with molecules of different structures and containing suitable donor atoms for metal-coordination (N, O, P). Then the ligands will be coordinated to Ruthenium-based skeletons with a known anticancer activity. Later on, analogous procedures may be employed for the preparation of new Pt, Os and Ir complexes based on intensively-investigated structures. The new metal complexes will be characterized by analytical, spectroscopic and electrochemical techniques. Then, they will be tested in vitro against a panel of cancer cell lines thus giving information about possible synthetic modifications for optimizing the drug action.
Several collaborations with Italian and foreign investigators/research groups are planned, in particular with Prof. Paul J. Dyson (EPFL, Lausanne), a "pioneer" of Ruthenium anticancer drugs.


Publications:
•    B. Campanella, M. Onor, L. Biancalana, A. D’Ulivo, E. Bramanti, Ovalbumin labeling with p-hydroxymercurybenzoate: The effect of different denaturing agents and the kinetics of reaction, Anal. Biochem. 2015, 483, 27-33.
•    L. Biancalana, M. Bortoluzzi, C. Forte, F. Marchetti, G. Pampaloni, Structural characterization of α-amino acid complexes of molybdates: a spectroscopic and DFT study, RSC Adv. 2015, 5, 9010-9018.
•    F. Marchetti, G. Pampaloni, L. Biancalana, Activation reactions of 1,1-dialkoxoalkanes and unsaturated O-donors by titanium tetrafluoride, Inorg. Chim. Acta 2012, 385, 135-139.


Conference proceedings:
•    G. Agonigi, L. Biancalana, P. J. Dyson, F. Marchetti, G. Pampaloni, E. Păunescu, T. Riedel, S. Zacchini, Synthesis and Antiproliferative Activity of New Ruthenium Complexes with Ethacrynic Acid-Modified Pyridine- and Triphenylphosphine-Ligands. XXI EuCOMC International Conference on Organometallic Chemistry, Bratislava, 5-9 July 2015 (poster presentation); X EuCOMC International School of Organometallic Chemistry, Camerino, 5-9 September 2015 (oral and poster presentation).
•    L. Biancalana, M. Bortoluzzi, C. Forte, F. Marchetti, G. Pampaloni, Dioxidomolybdenum(VI) complexes of α-Amino Acids. X EuCOMC International School of Organometallic Chemistry, Camerino, 5-9 September 2015 (poster presentation).