Molecules (Basel, Switzerland), 2022-01, Vol.27 (3), p.875
2022
Details
- Autor(en) / Beteiligte
- Titel
- Phenylalanine-Based AMPA Receptor Antagonist as the Anticonvulsant Agent with Neuroprotective Activity-In Vitro and In Vivo Studies
- Ist Teil von
- Molecules (Basel, Switzerland), 2022-01, Vol.27 (3), p.875
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2022
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Trying to meet the multitarget-directed ligands strategy, a series of previously described aryl-substituted phenylalanine derivatives, reported as competitive antagonists of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, were screened in vitro for their free-radical scavenging and antioxidant capacity in two different assays: ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity fluorescent (ORAC-FL) assays. The most active antioxidants and were further examined to evaluate their neuroprotective properties in vitro. In this study, compound showed a significant neuroprotective effect against the neurotoxin 6-hydroxydopamine in neuroblastoma SH-SY5Y and IMR-32 cell lines. Both compounds also showed prevention from high levels of reactive oxygen species (ROS) in SH-SY5Y cells. Furthermore, the desired monoamine oxidase B (MAO-B) inhibition effect (IC = 278 ± 29 nM) for was determined. No toxic effects up to 100 µM of and against neuroblastoma cells were observed. Furthermore, in vivo studies showed that compound demonstrated significant anticonvulsant potential in 6-Hz test, but in neuropathic pain models its antiallodynic and antihyperalgesic properties were not observed. Concluding, the compound seems to be of higher importance as a new phenylalanine-based lead candidate due to its confirmed promise in in vitro and in vivo anticonvulsant activity.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1420-3049eISSN: 1420-3049DOI: 10.3390/molecules27030875Titel-ID: cdi_doaj_primary_oai_doaj_org_article_30c4052d21b04e6595507df4b292cee4
- Format
- –
- Schlagworte
- 6-Hydroxydopamine, Alzheimer's disease, Amine oxidase (flavin-containing), Amino acids, AMPA antagonist, Amyotrophic lateral sclerosis, Animals, Anticonvulsants, Anticonvulsants - chemical synthesis, Anticonvulsants - chemistry, Anticonvulsants - pharmacology, antioxidant activity, Antioxidants, Biocompatibility, Blood-brain barrier, Brain research, Cell Line, Tumor, Cell lines, Convulsions & seizures, Drugs, Epilepsy, Fluorescence, Fluorescence recovery after photobleaching, FRAP, Humans, In vivo methods and tests, Ligands, Male, Mice, Monoamine Oxidase - metabolism, Monoamine Oxidase Inhibitors - chemical synthesis, Monoamine Oxidase Inhibitors - chemistry, Monoamine Oxidase Inhibitors - pharmacology, Nervous system, Neuroblasts, Neurological disorders, Neuroprotection, Neuroprotective Agents - chemical synthesis, Neuroprotective Agents - chemistry, Neuroprotective Agents - pharmacology, Neurotoxins, ORAC-FL, Oxidative stress, Oxidopamine - toxicity, Pain, Parkinson's disease, Phenylalanine, Phenylalanine - analogs & derivatives, Phenylalanine - chemical synthesis, Phenylalanine - chemistry, Phenylalanine - pharmacology, Receptors, AMPA - antagonists & inhibitors, Receptors, AMPA - metabolism, Scavenging, Toxicity, Toxins, α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors