Antonino Nicolò Fallica

Ciclo: XXXIV

Data inizio: 31/10/2018

Curriculum: Farmaceutiche

Borsa: UniCT

Titolo tesi: Targeting the Heme Oxygenase enzymatic system as a new approach for anticancer therapy

Abstract: The intrinsic complexity of the molecular mechanisms involved in tumor pathogenesis surely represents one of the main issues that contributes to the failure of common anticancer therapies. Current anticancer approaches are based on the application of different therapeutic protocols aimed at slowing down tumor growth and spread or at killing tumor cells. However, the polypharmacological approach usually applied, even if successful in some conditions, can give rise to cytotoxicity to healthy cells and trigger the appearance of chemoresistance phenomena. The modulation of the activity of biological targets specifically detectable in tumor cells could represent a valid approach for the definition of novel antitumor regimens. In this context, it has been discovered that beyond its physiological role, the inducible isoform of heme oxygenase (HO-1) contributes in the sustenance of a cytoprotective condition that is often exploited by cancer cells to survive and spread to healthy tissues. A wide plethora of studies proved that the specific inhibition of this enzyme is associated to reduced tumor growth and invasiveness, and it also contributes to reversal of chemoresistance. The present PhD thesis focuses on the design, synthesis and in vitro evaluation of novel classes of HO inhibitors with potential application in anticancer therapy. The research was carried out by the application of traditional and more innovative drug discovery approaches using as guidelines the information obtained by structure-activity relationship studies concerning HO inhibitors. In vitro enzymatic assays and biological studies led to the identification of potent compounds that could be used in the future for the design of selective inhibitors of HO-1 or HO-2, with the latter representing the constitutive enzymatic isoform. Finally, marked antiproliferative properties were discovered for a class of inhibitors charaterized by the presence of an acetamide function in the chemical structure of the molecule, with potential application for future in vivo studies.

Tutor: Pittalà

Data Conseguimento Titolo: 08/04/2022

Linkedin: Indicate il link

Email: antonio.fallica93@gmail.com

Periodi all'estero- Sede e data: Interdisciplinary Nanoscience Center (iNANO), Aarhus University,  14 June 2021‒28 January 2022 (7 mesi e mezzo)

Esperienze post-Dottorato ed attuale occupazione: Assegno di Ricerca presso DSFS – Università di Catania (27/06/2022‒26/12/2022). Assegno di Ricerca presso DSFS – Università di Catania (25/01/2023‒24/04/2023); Postdoctoral researcher presso Institute for Bioengineering of Catalonia (IBEC), Barcellona (Spagna) dal 01/05/2023