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; 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.

Graphical Abstract

Keywords:

• 2-(Quinoline-8-carboxamido)benzoic acid
• anthranilic acid
• dopaminergic neurodegeneration
• Parkinson’s disease
• Caenorhabditis elegans

Acknowledgments

The authors gratefully acknowledge the Center for Bio-Medical Engineering Core Facility for providing analytical equipment to Dankook University.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research was financially supported by the research fund of Dankook University in 2022.