Naphthoquinones as a Promising Class of Compounds for Facing the Challenge of Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is a degenerative disease that affects approximately 6.1 million people and is primarily caused by the loss of dopaminergic neurons. Naphthoquinones have several biological activities explored in the literature, including neuroprotective effects. Therefore, this review shows an overview of naphthoquinones with neuroprotective effects, such as shikonin, plumbagin and vitamin K, that prevented oxidative stress, in addition to multiple mechanisms. Synthetic naphthoquinones with inhibitory activity on the P2X7 receptor were also found, leading to a neuroprotective effect on Neuro-2a cells. It was found that naphthazarin can act as inhibitors of the MAO-B enzyme. Vitamin K and synthetic naphthoquinones hybrids with tryptophan or dopamine showed inhibition of the aggregation of α-synuclein. Synthetic derivatives of juglone and naphthazarin were able to protect Neuro-2a cells against neurodegenerative effects of neurotoxins. In addition, routes for producing synthetic derivatives were also discussed. With the data presented, 1,4-naphthoquinones can be considered as a promising class in the treatment of PD and this review aims to assist the scientific community in the application of these compounds. The derivatives presented can also support further research that explores their structures as synthetic platforms, in addition to helping to understand the interaction of naphthoquinones with biological targets related to PD.

Protection Activity of 1,4-Naphthoquinones in Rotenone-Induced Models of Neurotoxicity

“…Additionally, they inhibit enzymes involved in the generation of ROS, including NADPH oxidase in phagocytic cells, xanthine oxidase, mitochondrial cytochrome C oxidase, and microsomal monooxygenases. These effects can be attributed to the activation of the Keap1/Nrf2/ARE signaling pathway by 1,4-naphthoquinones, which help regulate the cellular redox status [18,22]. At the same time, we showed that U-443 and U-573 partially block NO formation in RAW 264.7 cells.…”

“…It has been established that these compounds possess a diverse range of biological activities, including antifungal, antibacterial, antioxidant, cardioprotective, hepatoprotective, anti-ischemic, and various other properties. There is an increasing number of scientific papers exploring the protective role of 1,4-naphthoquinones in disorders characterized by the degeneration of neurons such as AD and PD [10][11][12][13][14][15][16][17][18][19].…”

Effect of Hydroxytyrosol Derivatives of Donepezil on the Activity of Enzymes Involved in Neurodegenerative Diseases and Oxidative Damage

“…Confirming that acetylation, raising the size of the substituent groups, is only a medicinal chemistry tool to enhance membrane permeation [ 60 ]. The relevance of the results pointed to a leading approach for the identification of multitargeting hybrid compounds, a strategy receiving increased scientific interest in both neurodegenerative [ 61 , 62 , 63 ] and other diseases [ 64 ], including cancer [ 65 , 66 ].…”