Modeling Molecular Study between SDO1/Inhibitors: Search of New Treatments for Amyotrophic Lateral Sclerosis

Background: The Amyotrophic lateral sclerosis (ALS) is a degenerative and most frequent motor neuron disease characterized by the progressive impairment of upper and lower motor neurons. The treatment of the disease is still palliative and limited to the use of only two drugs, riluzole and edaravone, which only prolong survival by a few months. Taking into account the low number of therapy available for this disease, identification of novel therapeutic strategies for ALS is urgently needed. The superoxide dismutase 1 (SOD1) was the first gene in which mutations were found to be causative for the neurodegenerative disease and has been used as a promising target for the ALS treatment. Methods: In this work we used powerful computational tools (in silico method) such as Ligand-based Virtual Screening (SBVS), docking and molecular dynamics techniques to collaborate with the discovery of new candidates for more potent drugs to be used in the ALS disease treatment. Results: Compound 1 shows good stability in the active site of the SOD1 enzyme, with an intermolecular interaction energy of -154.80 kcal/mol. In addition, the presence of some amino acids such as Glu24, Glu21, Pro28, Lys23 and Lys30 is important for to maintain stability of this compound inside SOD1. Conclusion: This study was essential due to a low number of therapy available for this disease until the moment. With this study, it was possible to observe that Compound 1 is the most promising for the design of SOD1 mutant enzyme potential inhibitors. However, experimental tests in the SOD1 mutant to validate the inhibitory effect of Compound 1 will be required.