Natural compounds against neurodegenerative disorders
Alzheimer’s and Parkinson’s diseases are caused by inflammation of cells of the nervous system, eventually leading to a loss in synaptic function and communication. Treatment with neurotrophic proteins such as nerve growth factor that promote the growth of new neuronal cells has been hampered by poor delivery to the brain due to the blood brain barrier. Therefore, hydrophilic neurotrophic protein mimetics capable of crossing the blood brain barrier would be ideal. To address this issue, researchers of the EU-funded SYNEUROUT (Total synthesis of (2R)-hydroxy-norneomajucin and biological evaluation of neurite outgrowth) project proposed the utilisation of molecules extracted from natural products. Their work focused on the natural product (2R)-hydroxy-norneomajucin, which is isolated from fruits of the plant Illicium jiadifengpi and exhibits excellent neurite outgrowth-promoting activity. However, the extremely low extraction yield of the molecule hampered its pharmacological use. To overcome this hurdle, SYNEUROUT scientists turned to synthetic organic chemistry and optimised the first 12 steps of the total synthesis with an excellent overall yield. Considerable effort also went towards the establishment of neuronal cell assays to evaluate the neurite outgrowth abilities of several standard and unknown compounds. Collectively, the activities of the study emphasised the importance of natural products in drug discovery and set the basis for future research in the field. Next, researchers plan to perform structure-activity relationship studies to improve the activity of the compound, and identify its targets within the body. This would allow them to comprehend the mechanisms underlying the neuroprotective effect of (2R)-hydroxy-norneomajucin and potentially identify further compounds against the same targets.
Keywords
Natural compounds, neurodegenerative, SYNEUROUT, (2R)-hydroxy-norneomajucin, neurite outgrowth
