• Enzima Pin1

The enzyme Pin1 belongs to the Peptidyl-Prolyl Isomerase (PPIase) family, a class of enzymes that catalyze the cis/trans isomerization of peptide bonds involving a proline residue. Through isomerization, Pin1 induces conformational changes on target proteins, thereby regulating multiple physiological processes including cell growth, cell cycle regulation, immune response, neuronal differentiation and tumorigenesis. Recently, through a virtual screening procedure, a molecule, VS10, capable of inhibiting Pin1 has been identified. Structurally, VS10 includes a methylbenzofuran-2-carboxamide moiety, a thiophene carrying a carboxyl group and a phenyl ring. During my thesis period, I synthesized analogs of VS10, keeping the thiophene portion and phenyl ring constant and modifying the methylbenzofuran-2-carboxamide fragment. Specifically, the main scaffold benzofuran was replaced with medium-long chain aliphatic and aryl-aliphatic portions. In the last part of my thesis, I focused on another modification to be made to our reference compound. This time we kept the methylbenzofuran-2-carboxamide fragment constant and modified the phenyl portion bound to the aromatic heterocycle in particular substituents were introduced in the meta and para position of the phenyl ring.