Synthesis of Proposed Structure of Aaptoline B via Transition Metal-Catalyzed Cycloisomerization and Evaluation of Its Neuroprotective Properties in C. Elegans

Soobin Kim,Young-Taek Cha,Wooin Yang,Dong-Seok Han

doi:10.3390/app11199125

Soobin Kim, Young-Taek Cha + Show 2 more

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https://doi.org/10.3390/app11199125

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Journal: Applied sciences	Publication Date: Sep 30, 2021
Citations: 2	License type: CC BY 4.0

Affiliation: Dankook University, Woosuk University

Abstract

A concise synthesis of the proposed structure of aaptoline B, a pyrroloquinoline derived from a marine sponge, was accomplished. A key feature of this synthesis is the versatile transition metal-catalyzed cycloisomerization of N-propargylaniline to construct a quinoline skeleton. However, the spectral data of the synthesized aaptoline B did not agree with those of previous studies. The structure of the synthesized aaptoline B was confirmed using a combined 2D NMR analysis. Furthermore, we assessed the possible neuroprotective potential of aaptoline B using the C. elegans model system. In this study, aaptoline B significantly improved the viability and the morphology of dopaminergic neurons of nematodes under MPP+ exposure conditions. We also found that MPP+-induced motor deficits in nematodes were efficiently restored by aaptoline B treatment. Our findings demonstrate the neuroprotective effects of aaptoline B against MPP+-induced dopaminergic neuronal damage. Further studies are underway to explain its pharmacological mechanism.

Highlights

Parkinson’s disease (PD) is a progressive neurodegenerative disorder of the central nervous system that affects millions of people worldwide
Aaptoline B (1) has been reported as a pyrroloquinoline alkaloid isolated from the marine sponge Aaptos aaptos by a Chinese research group [4]
This paper describes the total synthesis of the proposed structure of 1 and its protective properties against MPP+-induced dopaminergic neuro2 of 8 degeneration using the Caenorhabditis elegans model, which offers an excellent environment for PD research

Summary

Introduction

Parkinson’s disease (PD) is a progressive neurodegenerative disorder of the central nervous system that affects millions of people worldwide. The underlying pathological mechanism of PD remains unknown, overproduction of reactive oxygen species (ROS) is considered a major trigger of neuronal death in the SNpc [2]. Neurotoxins such as 1-methyl-4-phenylpyridinium (MPP+ ) and. Indole and quinoline derivatives exhibit diverse biological activities, including anticancer and anti-neurodegenerative diseases. These two scaffolds, including their heterocycle-linked and fused analogs, have been considered important privileged scaffolds in drug discovery [5,6,7]

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