• Alzheimer's disease
• cancer
• Fyn
• SFKs

The Fyn protein, which belongs to the Src family of kinases (SFKs), is involved in many biological activities such as : growth factor and cytokine receptor signalling, integrin-mediated signalling, cell-cell adhesion, platelet activation, ion channel function, differentiation of oligodendrocytes and keratinocytes, T-cell and B-cell receptor signalling.
At first, this protein was taken into account for its involvement in some diseases of the central nervous system such as Alzheimer’s and other tauopathies. Fyn, indeed, phosphorylates the Tau protein at its amino-terminus on Tyr 18; phosphorylated Tau is one of the main components of neurofibrillary tangles that characterize Alzheimer’s disease.
Then, the involvement of Fyn was highlighted in the development and progression of cancer. The overexpression of this protein leads to morphological changes at the cellular level that underlie the development of cancer cells.
The inhibition of Fyn, for example, is associated with a decrease in cell growth; this protein, indeed, promotes the antiapoptotic activity of Akt. Moreover, Fyn participates in other processes involved in the development of malignancies, such as cell migration, which determines the metastatic disease, cell adhesion and EMT (epithelial-mesenchymal transition).
Because of all these functions , this protein became a very interesting pharmaceutical target for neurodegenerative pathologies and tumours.
During this thesis work, I synthesized some new molecules with potential inhibitory activity against Fyn.
The design of these compounds started with virtual screening studies performed on commercially available libraries of compounds to identify new Fyn inhibitors. Some of the resulting compounds proved to efficiently inhibit Fyn. Therefore we planned to synthesize some derivatives bearing the same central scaffold. The new compounds share the same 1,2,4-triazin-5(2H)-one scaffold, differing only for the presence of substituents on the two aromatic rings.