Synthesis and application of β-carbolines as novel multi-functional anti-Alzheimer’s disease agents
| Autor: | Jessica Soule, Chris Tran, William Horton, Nandor Kugyela, Béla Török, Harry LeVine, Swarada R. Peerannawar, Aditya Kulkarni, Marianna Török, Rekha Tulsan, Abha Sood |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Antioxidant Aché Amyloid beta medicine.medical_treatment Clinical Biochemistry Pharmaceutical Science Disease Fibril Biochemistry Oligomer Article Antioxidants Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Alzheimer Disease Drug Discovery medicine Cholinesterases Humans Molecular Biology Cholinesterase Amyloid beta-Peptides Anti alzheimer Dose-Response Relationship Drug Molecular Structure biology Organic Chemistry language.human_language Molecular Docking Simulation 030104 developmental biology chemistry Drug Design biology.protein language Molecular Medicine Cholinesterase Inhibitors 030217 neurology & neurosurgery Carbolines |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 27:232-236 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2016.11.067 |
| Popis: | The design, synthesis and assessment of β-carboline core-based compounds as potential multifunctional agents against several processes that are believed to play a significant role in Alzheimer's disease (AD) pathology, are described. The activity of the compounds was determined in Aβ self-assembly (fibril and oligomer formation) and cholinesterase (AChE, BuChE) activity inhibition, and their antioxidant properties were also assessed. To obtain insight into the mode of action of the compounds, HR-MS studies were carried out on the inhibitor-Aβ complex formation and molecular docking was performed on inhibitor-BuChE interactions. While several compounds exhibited strong activities in individual assays, compound 14 emerged as a promising multi-target lead for the further structure-activity relationship studies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect