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

Abstract

2-(Quinoline-8-carboxamido)benzoic acid (2-QBA;) is a natural quinoline alkaloid isolated from the deep-sea-derived fungussp. SCSIO06786. Alkaloidwas synthesized by an amidation reaction of 8-quinolinecaroxylic acid with methyl anthranilate, followed by hydrolysis. The neuroprotective properties of 1 were evaluated using aParkinson's disease model, which revealed thatsignificantly 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. We further demonstrated that treatment withmodulates the formation of neurotoxic α-synuclein oligomers by suppressing α-synuclein expressions and enhancing proteasome activity. These results suggest thatis a promising therapeutic candidate for the treatment of Parkinson's disease.