γ-Secretase Inhibitors Selected by Molecular Docking, to Develop a New Drug Against Alzheimer's Disease.
| Autor: | Trasviña-Arenas CH; Research Center on Aging, Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV), Calzada de los Tenorios No. 235, 14330, Mexico City, Mexico., Ayala Medina LA; School of Medicine Campus Mexicali, Autonomous University of Baja California, Mexicali, 21000, BC, México., Vique-Sánchez JL; School of Medicine Campus Mexicali, Autonomous University of Baja California, Mexicali, 21000, BC, México. |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | Reports of biochemistry & molecular biology [Rep Biochem Mol Biol] 2023 Jul; Vol. 12 (2), pp. 340-349. |
| DOI: | 10.61186/rbmb.12.2.340 |
| Abstrakt: | Background: Alzheimer´s disease (AD) is one of the most common forms of dementia, is characterized by memory loss and cognitive impairment that affects more than 30 million people worldwide. The pathogenesis of Alzheimer's disease is primary driven by brain accumulation of the amyloid β peptide generated from the amyloid-β precursor protein (APP) via cleavages by β- and γ-secretase. In this study, we propose an approach by molecular docking to select compounds as γ-secretase inhibitors for decreasing the APP generation. Methods: We selected potential γ-secretase inhibitors by molecular docking in the potential site between Asp257, Lue268, Asp385, Ile387, Phe388, and Leu432 amino acids in presenilin-1 (PS-1), using a chemical library of over 500,000 compounds. Results: Eight compounds (AZ1 - AZ8) were selected by molecular docking to develop γ-secretase inhibitors for decreasing the APP generation. Conclusions: AZ1 - AZ8 compounds could be interacting in the potential site between Asp257, Lue268, Asp385, Ile387, Phe388, and Leu432 amino acids in PS-1. These compounds could specifically interact in the binding pocket in PS-1 to prevent/decrease the APP generation, to develop a new drug against Alzheimer's disease. Competing Interests: The authors declare no conflicts of interest. |
| Databáze: | MEDLINE |
| Externí odkaz: |
|