《Novel Curcumin-Diethyl Fumarate Hybrid as a Dualistic GSK-3β Inhibitor/Nrf2 Inducer for the Treatment of Parkinson’s Disease》 was published in ACS Chemical Neuroscience in 2020. These research results belong to Di Martino, Rita Maria Concetta; Pruccoli, Letizia; Bisi, Alessandra; Gobbi, Silvia; Rampa, Angela; Martinez, Ana; Perez, Concepcion; Martinez-Gonzalez, Loreto; Paglione, Maria; Di Schiavi, Elia; Seghetti, Francesca; Tarozzi, Andrea; Belluti, Federica. Synthetic Route of C5H6O2 The article mentions the following:
Common copathogenic factors, including oxidative stress and neuroinflammation, are found to play a vital role in the development of neurodegenerative disorders, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Nowadays, owing to the multifactorial character of the diseases, no effective therapies are available, thus underlying the need for new strategies. Overexpression of the enzyme GSK-3β and downregulation of the Nrf2/ARE pathway are responsible for a decrease in antioxidant defense effects. These pieces of evidence underline the usefulness of dual GSK-3β inhibitors/Nrf2 inducers. In this regard, to design a dual modulator, the structures of a curcumin-based analog, as GSK-3β inhibitor, and a di-Et fumarate fragment, as Nrf2 inducer, were combined. Among the hybrids, 5 and 6 proved to effectively inhibit GSK-3β, while 4 and 5 showed a marked ability to activate Nrf2 together to increase the neuronal resistance to oxidative stress. These last pieces of evidence translated into specific neuroprotective effects of 4 and 5 against PD pathol. events including neurotoxicity elicited by α-synuclein aggregates and 6-hydroxydopamine. Hybrid 5 also showed neuroprotective effects in a C. elegans model of PD where the activation of GSK-3β is intimately involved in Nrf2 regulation. In summary, 5 emerged as an interesting multitarget derivative, valuable to be exploited in a multitarget PD perspective. After reading the article, we found that the author used Ethyl propiolate(cas: 623-47-2Synthetic Route of C5H6O2)
Ethyl propiolate(cas: 623-47-2) is a clear colorless to pale yellow liquid that is soluble in ethanol, ether and chloroform. It an important organic chemical raw material and pharmaceutical intermediate. Ethyl propargylate is obtained by oxidation of propargyl alcohol to propargylic acid followed by esterification.Synthetic Route of C5H6O2
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics