Structural understanding of 5-(4-hydroxy-phenyl)-N-(2-(5-methoxy-1H-indol-3-yl)-ethyl)-3-oxopentanamide as a neuroprotectant for Alzheimer’s disease
| Autor: | Jakob Green, Glen E. Kellogg, Yuqi Jiang, Yiming Xu, John M. Saathoff, Shijun Zhang |
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| Rok vydání: | 2021 |
| Předmět: |
Stereochemistry
Clinical Biochemistry Pharmaceutical Science Ring (chemistry) 01 natural sciences Biochemistry Neuroprotection Article Cell Line Structure-Activity Relationship chemistry.chemical_compound Alzheimer Disease Drug Discovery medicine Humans Moiety Molecular Biology Indole test Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Organic Chemistry 0104 chemical sciences 010404 medicinal & biomolecular chemistry Neuroprotective Agents Mechanism of action chemistry Docking (molecular) Molecular Medicine medicine.symptom Lead compound Mitochondrial Complex I |
| Zdroj: | Bioorg Med Chem Lett |
| ISSN: | 0960-894X |
| Popis: | In our continuing efforts to develop novel neuroprotectants for Alzheimer’s disease (AD), a series of analogs based on a lead compound that was recently shown to target the mitochondrial complex I were designed, synthesized and biologically characterized to understand the structure features that are important for neuroprotective activities. The results from a cellular AD model highlighted the important roles of the 4-OH on the phenyl ring and the 5-OCH(3) on the indole ring of the lead compound. The results also demonstrated that the β-keto moiety can be modified to retain or improve the neuroprotective activity. Docking studies of selected analogs to the FMN site of mitochondrial complex I also supported the observed neuroprotective activities. Collectively, the results provide further information to guide optimization and development of analogs based on this chemical scaffold as neuroprotectants with a novel mechanism of action for AD. |
| Databáze: | OpenAIRE |
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