| Title : Benzofurans as acetylcholinesterase inhibitors for treating Alzheimer's disease: synthesis, in vitro testing, and in silico analysis - Coaviche-Yoval_2024_ChemMedChem__e202300615 |
| Author(s) : Coaviche-Yoval A , Tovar-Miranda R , Rodriguez JE , Lagos-Cruz JA , Luna H , Andrade-Jorge E , Trujillo-Ferrara JG |
| Ref : ChemMedChem , :e202300615 , 2024 |
| Abstract : Alzheimer's disease (AD) is a neurodegenerative disorder and the leading cause of dementia worldwide. It is characterized by a progressive decline in cholinergic neurotransmission. During the development of AD, acetylcholinesterase (AChE) binds to beta-amyloid peptides to form amyloid fibrils, which aggregate into plaque deposits. These complexes are cytotoxic for the brain, causing impairment of memory, attention, and cognition. AChE inhibitors are the main treatment for AD, but their effect is only palliative. This study aimed to design and synthesize novel benzofuran derivatives and evaluate their inhibition of AChE in vitro and in silico. Results: The seven synthesized benzofuran derivatives inhibited AChE in vitro. Benzofurans hydroxy ester 4, amino ester 5, and amido ester (+/-)-7 had the lowest inhibition constant (Ki) values and displayed good affinity for EeAChE in molecular docking. Six derivatives showed competitive inhibition, while the best compound (5: Ki = 36.53 mM) exhibited uncompetitive inhibition. The amino, hydroxyl, amide, and ester groups of the ligands favored interaction with the enzyme by hydrogen bonds. Conclusion: Three benzofurans were promising AChE inhibitors with excellent Ki values. In future research on their their application to AD, 5 will be considered as the base structure. |
| ESTHER : Coaviche-Yoval_2024_ChemMedChem__e202300615 |
| PubMedSearch : Coaviche-Yoval_2024_ChemMedChem__e202300615 |
| PubMedID: 38554286 |
Coaviche-Yoval A, Tovar-Miranda R, Rodriguez JE, Lagos-Cruz JA, Luna H, Andrade-Jorge E, Trujillo-Ferrara JG (2024)
Benzofurans as acetylcholinesterase inhibitors for treating Alzheimer's disease: synthesis, in vitro testing, and in silico analysis
ChemMedChem
:e202300615
Coaviche-Yoval A, Tovar-Miranda R, Rodriguez JE, Lagos-Cruz JA, Luna H, Andrade-Jorge E, Trujillo-Ferrara JG (2024)
ChemMedChem
:e202300615