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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.

Synthesis of a natural quinoline alkaloid isolated from the deep-sea-derived fungus and its potential as a therapeutic for Parkinson’s disease