Synthesis of a natural quinoline alkaloid isolated from the deep-sea-derived fungus and its potential as a therapeutic for Parkinson's disease.
J Asian Nat Prod Res
; 25(5): 446-455, 2023 May.
Article
em En
| MEDLINE
| ID: mdl-35980025
ABSTRACT
2-(Quinoline-8-carboxamido)benzoic acid (2-QBA; 1) is a natural quinoline alkaloid isolated from the deep-sea-derived fungus Aspergillus sp. SCSIO06786. Alkaloid 1 was synthesized by an amidation reaction of 8-quinolinecaroxylic acid with methyl anthranilate, followed by hydrolysis. The neuroprotective properties of 1 were evaluated using a Caenorhabditis elegans Parkinson's disease model, which revealed that 1 significantly ameliorated 1-methyl-4-phenylpyridinium (MPP+)-induced dopaminergic neurodegeneration in a dose-dependent manner. MPP+-induced behavioral defects in worms, including impaired locomotion and basal slowing ability, were restored by treatment with 1. We further demonstrated that treatment with 1 modulates the formation of neurotoxic α-synuclein oligomers by suppressing α-synuclein expressions and enhancing proteasome activity. These results suggest that 1 is a promising therapeutic candidate for the treatment of Parkinson's disease.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
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Quinolinas
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Fármacos Neuroprotetores
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Alcaloides
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article