Radwan, A.; Alanazi, F.; Abdel Rahman, A.M. Design, Synthesis and Molecular Modeling of Benzofuran-8-Hyroxyquinoline Hybrids as Multi-Target Inhibitors and Potential Anti-Alzheimer’s Disease. Preprints2024, 2024020731. https://doi.org/10.20944/preprints202402.0731.v1
APA Style
Radwan, A., Alanazi, F., & Abdel Rahman, A.M. (2024). Design, Synthesis and Molecular Modeling of Benzofuran-8-Hyroxyquinoline Hybrids as Multi-Target Inhibitors and Potential Anti-Alzheimer’s Disease. Preprints. https://doi.org/10.20944/preprints202402.0731.v1
Chicago/Turabian Style
Radwan, A., Fars Alanazi and Anas M. Abdel Rahman. 2024 "Design, Synthesis and Molecular Modeling of Benzofuran-8-Hyroxyquinoline Hybrids as Multi-Target Inhibitors and Potential Anti-Alzheimer’s Disease" Preprints. https://doi.org/10.20944/preprints202402.0731.v1
Abstract
Cholinesterase (ChE) and secretase (BACE) inhibitors, and fibril- and β-amyloid-suppressing medicines are used to treat Alzheimer's disease (AD) symptomatically. The prevalence and complex nature of AD have increased the urgent need for multi-targeted directed ligands (MTDLs). This is because MTDLs can prevent potential drug-drug interactions during poly-therapy and have a better therapeutic profile than single targeted agents. Using piperazine linker or spacer and two primary scaffolds, benzofuran and 8-hydroxyquinoline, a unique class of multi-targeted medicines was recently reported by our group. These compounds showed re-markable effectiveness in inhibiting Aβ1-42 aggregation and acting as iron chelators.The results prompted us to synthesize an additional series of compounds as multimodal anti-AD agents and investigate its inhibitor activities to ChE (AChE/BChE) and BACE1 enzymes. The resulting in-hibitory effects suggested that the compounds under study might be used to improve cognitive function. The docking analysis' findings revealed that the compounds bind to AChE and BChE by forming H-bond interactions with amino acid residues at binding sites and µ-stacking inter-actions with aromatic residues, whereas the binding to BACE1 only revealed H-bond interac-tions with amino acid residues at binding sites.
Chemistry and Materials Science, Medicinal Chemistry
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
