Chemists of the Ural Federal University and the Sri Venkateswar University (Tirupati, India) have synthesized new neuroprotective antioxidants based on derivatives of α-methyl-L-DOPA and urea. The results of the research are presented in the journal Bioorganic Chemistry.
«Cells of the peripheral nervous system are able to convert L-DOPA into dopamine, but its accumulation in the peripheral nervous system, for example, in Parkinson’s disease, leads to undesirable side effects. Therefore, a good clinical practice is use of L-DOPA in combination with carbidopa, an inhibitor of DOPA decarboxylase” explains Grigory Zyryanov, co-author of the article, professor at the Department of Organic and Biomolecular Chemistry of UrFU. – In this study, we use urea derivatives based on α-methyl-L-DOPA, (S) -2-amino-3- (3, 4-dihydroxyphenyl) -2-methylpropionic acid, an analogue of L-DOPA and carbidopa. In this case, as a donor of hydrogen bonds, urea acts as an additional coordinating fragment and helps to keep the drug compound in the neuron receptors responsible for the oxidative process».
During the research, the Ural and Indian chemists have compared which of the α-methyl-L-DOPA and urea compounds successfully overcome the blood-brain barrier and exhibit the greatest antioxidant activity, allowing to prevent and eliminate the pathogenic effects of oxidative stress.
These data indicate that good prospects for the use of compounds as components of drugs: in accordance with the Lipinski’s Rule, the compounds have no more than 5 groups of hydrogen bond donors, no more than 10 groups of hydrogen bond acceptors, have a molecular weight less than 500 daltons (more heavy substance does not overcome the blood-brain barrier) and, finally, have a high solubility in water and octanol.
The next stage of work is in vitro and in vivo studies into the biological activity of the compounds. The scientists want to identify potential candidates for the role of medicinal antioxidants, to determine routes of drug administration: tablets, capsules, intravenous or intramuscular injection or inhalation.