The project embraces the discovery of NCEs acting as single or multitarget agents toward classic and non-classic therapeutics targets of neurodegenerative diseases (Alzheimer’s Disease, Parkinson’s Disease and Amyotrophic Lateral Sclerosis).

The project is supported by the network of the COST Action – CA15135 Multi-target paradigm for innovative ligand identification in the drug discovery process (MuTaLig) and by national projects, namely Mito4ALS – Development of Novel Mitochondria-Targeted Antioxidants for Improving SOD1-Familial Amyotrophic Lateral Sclerosis Phenotype (POCI-01-0145-FEDER-02939) and COMT4BRAIN-Development of Centrally-Active and Safe Catechol O-Methyltransferase Inhibitors (POCI-01-0145-FEDER-29164). The international and national networks ensure the mandatory computational drug design and in vivo assays.

Selected publications

  • Reis J, Manzella N, Cagide F, Mialet-Perez J, Uriarte E, Parini A, Borges F, Binda C. Tight-Binding Inhibition of Human Monoamine Oxidase B by Chromone Analogs: A Kinetic, Crystallographic, and Biological Analysis. J Med Chem. 2018; 61(9):4203-4212.
  • Silva T, Mohamed T, Shakeri A, Rao PP, Martínez-González L, Pérez DI, Martínez A, Valente MJ, Garrido J, Uriarte E, Serrão P, Soares-da-Silva P, Remião F, Borges F. Development of Blood-Brain Barrier Permeable Nitrocatechol-Based Catechol O-Methyltransferase Inhibitors with Reduced Potential for Hepatotoxicity. J Med Chem. 2016; 59(16):7584-97.
  • Reis J, Cagide F, Chavarria D, Silva T, Fernandes C, Gaspar A, Uriarte E, Remião F, Alcaro S, Ortuso F, Borges F. Discovery of New Chemical Entities for Old Targets: Insights on the Lead Optimization of Chromone-Based Monoamine Oxidase B (MAO-B) Inhibitors. J Med Chem. 2016; 59(12):5879-93.