Scientists Get Closer to Curing Alzheimer's and Parkinson's Diseases

10:35, March 31, 2023

The developed compounds are of particular interest for medicinal chemistry

Prospective compounds for the treatment of neurodegenerative diseases have been synthesized by Russian scientists. The compounds are of great interest for medicinal chemistry, especially for the development of treatments for Alzheimer's and Parkinson's diseases.

According to Timofey Moseev, a member of the group and an employee of the UrFU Chemical Pharmaceutical Center, the researchers managed to test the toxicity of the compounds in vitro on the kidney cells of a healthy human embryo. The researchers used the strategy of nucleophilic hydrogen substitution (a substitution reaction in which the substrate is attacked by a nucleophile, a reagent that carries a pair of unshared electrons). The process does not require metal catalysis, which is particularly important in the production of biologically active compounds, where any metal impurity can significantly distort toxicity and activity data.

To assess the ability of the synthesized molecules to bind to biotargets (proteins that play an important role in a particular disease), the researchers conducted experiments using docking - a molecular modeling technique. Docking allows predicting with a certain probability how a molecule interacts with targeted proteins.

"Our research includes molecular design and directed synthesis of a series of new azaheterocyclic compounds containing imidazole and indole fragments, digital modeling of biotarget interactions, and toxicity assessment in cell lines," says Timofey Moseev, UrFU Associate Professor. - The resulting compounds proved to have a high affinity for the targeted proteins responsible for causing neurodegenerative diseases, as well as low toxicity. This is only the first stage in the development of compounds for the treatment of these pathologies. In the future, it will be necessary to evaluate their efficacy on proteins, and research is already underway in this direction".

The research is carried out by the staff of the Institute of Chemical Engineering of the Ural Federal University in cooperation with colleagues from the Ural and Siberian Branches of the Russian Academy of Sciences and the Ural Medical University.

The results are published in a special issue of the journal New Research on Transition Metal Catalysis and Green Synthesis.

Reference 

Neurodegenerative diseases are a group of diseases associated with the progressive death of nerve cells.

In Russia, the incidence of dementia, Parkinson's disease and Alzheimer's disease will reach the epidemiological threshold of 5% of the population by 2050, according to the Bekhtereva Human Brain Institute. Meanwhile, the incidence of multiple sclerosis is increasing worldwide.