Neuroprotective effects of prenylated flavanones isolated from Dalea species, in vitro and in silico studies
| Autor: | José Luis Cabrera, Carolina Echeverry, Mariana Andrea Peralta, Florencia Arredondo, Diego Carvalho, Eduardo Savio, Juan Andrés Abin-Carriquiry, María Gabriela Ortega, Giselle Prunell, María D. Santi |
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| Rok vydání: | 2020 |
| Předmět: |
In silico
Pharmacology 01 natural sciences Neuroprotection PC12 Cells 03 medical and health sciences Structure-Activity Relationship Prenylation Drug Discovery medicine Animals Computer Simulation 030304 developmental biology chemistry.chemical_classification Neurons 0303 health sciences biology 010405 organic chemistry Chemistry Organic Chemistry Neurodegeneration Cell Differentiation Fabaceae General Medicine biology.organism_classification medicine.disease In vitro 0104 chemical sciences Rats Oxidative Stress Enzyme Neuroprotective Agents Flavanones Dalea |
| Zdroj: | European journal of medicinal chemistry. 206 |
| ISSN: | 1768-3254 |
| Popis: | Neurodegenerative diseases (NDs) represent a global problem on public health, with a growing incidence as human longevity increases. Currently, although there are palliative strategies available for most of these diseases, there is a lack of effective therapies for their cure. Flavonoids are extensively studied for their multi-target behavior. Among numerous biological activities, it has been reported that they act at the CNS level, presenting neuroprotective activity through different mechanisms of action. Dalea L. (Fabaceae) is an American genus, with about 172 species. Dalea elegans Gillies ex. Hook. & Arn and Dalea pazensis Rusby, both South American species, are the important source of natural compounds of the prenylated flavanones type. In the present study, five prenylated flavanones isolated from Dalea species were assayed for their neuroprotective activity in two in vitro models of neurodegeneration. Flavanones 1 and 2 exhibited neuroprotective effects against oxidative stress-induced death in both models, granular cerebellar neurons and (NGF)-differentiated PC12 cells. Structure-activity relationships were also reported. Our results indicated that an 8-prenyl group at the A-ring accompanied by an unsubstituted B-ring, or a 2’,4’-dihydroxy-5’-dimethylallyl substitution, lead to the most potent flavanones. Furthermore, in silico studies were performed, and several putative targets in NDs were identified for compounds 1 and 2. Between them, the enzyme acetylcholinesterase was selected for its validation in vitro. The present in vitro and in silico results imply that prenylated flavanones 1 and 2 may be useful in the development and design of future strategies for the treatment of NDs diseases. |
| Databáze: | OpenAIRE |
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