Disseny de nous agents terapeútics que interfereixen en mecanismes cel·lulars de transducció de senyals: Els receptors de serotonina i cannabinoides i el domini SH2 de Grb2

The main goal of this project is to develop new agents targeting signalling pathways: (A) classic neurotransmission (serotonin 5-HT1A, 5-HT6 and 5-HT7 receptors), (B) lipid signalling (anandamide transporter, cannabinoid CB1 and CB2 receptors) and (C) mitogen signalling (interaction between the HER2 receptor and the SH2 domain of Grb2). This will be achieved using an approach that combines theoretical (molecular modelling and computer assisted drug design) and experimental (organic synthesis and biological evaluation) procedures.A, B) The design of compounds interacting with serotoninergic and cannabinoid receptors will be carried out through the development of models of pharmacophore, 3D-QSAR/CoMFA, and ligand-receptor complexes. The synthesis and biological evaluation of their affinity and selectivity will be performed with the aim of developing new agents with clinical utility for the treatment of several disorders in which the central and peripheral nervous systems are involved.C) With respect to the HER2 receptor, once the compounds have been designed using molecular modeling from the known crystal structures, the synthesis and biological evaluation of new nonpeptidic inhibitors of the interaction between the HER2 receptor and SH2 domain of Grb2 will be carried out in order to develop new antitumor agents.