Synthesis, bioactivity and molecular modeling studies on potential anti-Alzheimer piperidinehydrazide-hydrazones
| Autor: | Ayse Hande Tarikogullari, Ercin Erciyas, Sumru Sozer Karadagli, Ulrike Holzgrabe, Vildan Alptüzün, Sülünay Parlar, Gozde Sayar |
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| Rok vydání: | 2019 |
| Předmět: |
Models
Molecular Antioxidant Molecular model medicine.medical_treatment Hydrazone 01 natural sciences Biochemistry Antioxidants Structure-Activity Relationship chemistry.chemical_compound Picrates Piperidines Alzheimer Disease Drug Discovery medicine Animals Humans Benzothiazoles Horses Molecular Biology Butyrylcholinesterase chemistry.chemical_classification Amyloid beta-Peptides Dose-Response Relationship Drug Molecular Structure biology 010405 organic chemistry Biphenyl Compounds Organic Chemistry Hydrazones Active site Acetylcholinesterase In vitro 0104 chemical sciences 010404 medicinal & biomolecular chemistry Neuroprotective Agents Enzyme chemistry Electrophorus biology.protein Cholinesterase Inhibitors Sulfonic Acids |
| Zdroj: | Bioorganic Chemistry. 87:888-900 |
| ISSN: | 0045-2068 |
| DOI: | 10.1016/j.bioorg.2018.11.051 |
| Popis: | A group of N-benzylpiperidine-3/4-carbohydrazide-hydrazones were designed, synthesized and evaluated for acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) activities, Aβ42 self-aggregation inhibitory potentials, and antioxidant capacities, in vitro. All of the compounds displayed eeAChE and huAChE inhibitory activity in a range of IC50 = 5.68–11.35 µM and IC50 = 8.80–74.40 µM, respectively and most of the compounds exhibited good to moderate inhibitory activity on BuChE enzyme. Kinetic analysis and molecular modeling studies were also performed for the most potent compounds (1g and 1j). Not only the molecular modeling studies but also the kinetic analysis suggested that these compounds might be able to interact with the catalytic active site (CAS) and the peripheral anionic site (PAS) of the enzymes. In the light of the results, compound 1g and compound 1j may be suggested as lead compounds for multifunctional therapy of AD. |
| Databáze: | OpenAIRE |
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