Design, Synthesis, Development and HTS of libraries of small molecules as modulators of proteins involved in infective pathologies, cancer, arthritis, cardiovascular diseases, neuro-degeneration/regeneration, depression. Development of probes for molecular imaging [ligand labeling of our leads with fluorophores, F18 (Pet) or cages for metal ions (MRI), use of gold (or iron) nanoparticles]. Our molecules are heterocycles, peptidomimetics or unnatural sugars developed as: a) modulators of metalloenzyme activity (Human MMPs , Adams, ADAMTS and Meprins, and some metalloproteases of nosocomial microorganism), b) Inhibitors of Human and Bacterial Serine Proteases (HNE, Bacterial Transpeptidases and Beta-Lactamases), c) Inhibitors of Transthyretin misfolding, d) Ligands of G-proteins (Adrenergic and Dopaminergic ), e) Inhibitors of Serotonin, Dopamine and Norepinephrine Transporters, f) Inhibitors of Fungal Demethylases, h) Inhibitors of MDM2-p53 interaction, i) Modulators of Carbonic Anhydrases (CAs-Inhibitors/Activators).