Identification of cellular targets and molecular action mechanism of newly synthesized metal complexes

Abstract

The end goal of this project is the study of the biological activity of newly synthesized compounds, members of the class of thiosemicarbazones. They are widely studied for their pharmaceutical properties and possess antitumor, antibacterial, antifungal and antiviral activities. This research can be divided into two sections. In the first one, the aim was to identify thiosemicarbazone derivates as antifungal agents. This part belongs to the “Aflatox project”, which purpose is the design and the synthesis of new types of inhibitors of proliferation and aflatoxins production of Aspergillus flavus. In this context, we studied the cytotoxic and genotoxic activities of antimycotoxigenic molecules on human healthy cell lines. In the second one, the aim was to identify thiosemicarbazone derivates as anticancer agents. In particular, we focused on the biological activity of citronellal thiosemicarbazones coordinated with three different metals: nickel, platinum and copper. We performed in vitro studies on human cancer cell lines and on primary tumour samples to identify metal complex cytotoxic and genotoxic activities. In addition, we analysed specific cellular pathways after the treatment with the compounds in order to identify their cellular targets and molecular action mechanisms. Furthermore, all the results were used to evaluate their structure/activity relationships.