Derivatives of caffeic acid, a natural antioxidant, as the basis for the discovery of novel nonpeptidic neurotrophic agents

Bioorganic & Medicinal Chemistry
Fatemeh MoosaviOmidreza Firuzi

Abstract

Neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease, threaten the lives of millions of people and the number of affected patients is constantly growing with the increase of the aging population. Small molecule neurotrophic agents represent promising therapeutics for the pharmacological management of neurodegenerative diseases. In this study, a series of caffeic acid amide analogues with variable alkyl chain lengths, including ACAF3 (C3), ACAF4 (C4), ACAF6 (C6), ACAF8 (C8) and ACAF12 (C12) were synthesized and their neurotrophic activity was examined by different methods in PC12 neuronal cells. We found that all caffeic acid amide derivatives significantly increased survival in PC12 neuronal cells in serum-deprived conditions at 25μM, as measured by the MTT assay. ACAF4, ACAF6 and ACAF8 at 5µM also significantly enhanced the effect of nerve growth factor (NGF) in inducing neurite outgrowth, a sign of neuronal differentiation. The neurotrophic effects of amide derivatives did not seem to be mediated by direct activation of tropomyosin receptor kinase A (TrkA) receptor, since K252a, a potent TrkA antagonist, did not block the neuronal survival enhancement effect. Similarly, the active compounds did not...Continue Reading

Citations

Jan 8, 2019·Critical Reviews in Food Science and Nutrition·Raffaella Colombo, Adele Papetti
Aug 29, 2019·Critical Reviews in Food Science and Nutrition·Anurag Khatkar, Krishna Kant Sharma
Dec 20, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Razieh HosseiniOmidreza Firuzi
Apr 29, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Kouadio Ibrahime SinanGiustino Orlando

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