Chalcones as Potential Ligands for the Treatment of Parkinson’s Disease

Abstract

Along with the increase in life expectancy, a significant increase of people suffering from neurodegenerative diseases (ND) has been noticed. The second most common ND, after Alzheimer’s disease, is Parkinson’s disease (PD), which manifests itself with a number of motor and non-motor symptoms that hinder the patient’s life. Current therapies can only alleviate those symptoms and slow down the progression of the disease, but not effectively cure it. So now, in addition to understanding the mechanism and causes of PD, it is also important to find a powerful way of treatment. It has been proved that in the etiology and course of PD, the essential roles are played by dopamine (DA) (an important neurotransmitter), enzymes regulating its level (e.g., COMT, MAO), and oxidative stress leading to neuroinflammation. Chalcones, due to their “simple” structure and valuable biological properties are considered as promising candidates for treatment of ND, also including PD. Here, we provide a comprehensive review of chalcones and related structures as potential new therapeutics for cure and prevention of PD. For this purpose, three databases (Pubmed, Scopus and Web of Science) were searched to collect articles published during the last 5 years (January 2018–February 2022). Chalcones have been described as promising enzyme inhibitors (MAO B, COMT, AChE), α-synuclein imaging probes, showing anti-neuroinflammatory activity (inhibition of iNOS or activation of Nrf2 signaling), as well as antagonists of adenosine A1 and/or A2A receptors. This review focused on the structure–activity relationships of these compounds to determine how a particular substituent or its position in the chalcone ring(s) (ring A and/or B) affects biological activity.

The cytosolic DNA‐sensing cGAS–STING pathway in neurodegenerative diseases

“…The main pathological change in PD is the degeneration and death of dopaminergic neurons in the substantia nigra area, which leads to a decrease in dopamine content in the ventral striatum and the dysfunction of motor regulation and cognitive impairment. Dopamine (DA), dopaminergic neuron cell death, oxidative stress, and neuroinflammation have been shown to play significant roles in the pathogenesis of PD 83,84 . The cGAS‐STING pathway is most likely to be activated during the progression of PD, as injured dopaminergic neurons can produce dsDNA.…”

“…Dopamine (DA), dopaminergic neuron cell death, oxidative stress, and neuroinflammation have been shown to play significant roles in the pathogenesis of PD. 83,84 The cGAS-STING pathway is most likely to be activated during the progression of PD, as injured dopaminergic neurons can produce dsDNA. Some experimental data have been supporting this theory in recent years.…”

Alzheimer’s Disease: Understanding Its Novel Drug Delivery Systems and Treatments

“…They also have a high inhibitory potential on the monoamine oxidase B, catechol-O-methyltransferase, and acetylcholine enzymes. Simple alterations within the A and/or B rings can produce such consequences [ 33 ].…”

Development of a New Class of Monoamine Oxidase-B Inhibitors by Fine-Tuning the Halogens on the Acylhydrazones

“…Many scaffolds, such as coumarins, isatins, chalcones, and hydrazones, are used to target both MAO-A and MAO-B. − This particular research focuses on the hydrazone moiety, which has been widely reported to inhibit MAO-B activity. The N-acylhydrazone moiety can serve as a ligand for various receptor types.…”