Discovery of sustainable drugs for Alzheimer's disease: cardanol-derived cholinesterase inhibitors with antioxidant and anti-amyloid properties
| Autor: | Ondřej Soukup, Monica Abreu, Elisa Uliassi, Giselle de Andrade Ramos, Maria Laura Bolognesi, Alessandra S. Kiametis, Paul E. Fraser, Ling Wu, Irene Liparulo, Christian Bergamini, Luiz Antonio Soares Romeiro, Marina Naldi, Edilberto R. Silveira, Guilherme D. Brand, Jan Korábečný, Manuela Bartolini, Ricardo Gargano, Lukas Prchal, Andressa Souza de Oliveira |
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| Přispěvatelé: | Ramos, GD, de Oliveira, AS, Bartolini, M, Naldi, M, Liparulo, I, Bergamini, C, Uliassi, E, Wu, L, Fraser, PE, Abreu, M, Kiametis, AS, Gargano, R, Silveira, ER, Brand, GD, Prchal, L, Soukup, O, Korabecny, J, Bolognesi, ML, Romeiro, LAS |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Antioxidant
medicine.medical_treatment Pharmaceutical Science Biochemistry Ferulic acid 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Drug Discovery medicine Alzheimer's disease sustainable drugs cardanol derivatives cholinesterase inhibitors antioxidant amyloid Butyrylcholinesterase 030304 developmental biology ADME Cholinesterase Pharmacology chemistry.chemical_classification 0303 health sciences Cardanol Reactive oxygen species biology Organic Chemistry Acetylcholinesterase Chemistry chemistry biology.protein Molecular Medicine 030217 neurology & neurosurgery |
| Zdroj: | RSC Med Chem |
| Popis: | As part of our efforts to develop sustainable drugs for Alzheimer's disease (AD), we have been focusing on the inexpensive and largely available cashew nut shell liquid (CNSL) as a starting material for the identification of new acetylcholinesterase (AChE) inhibitors. Herein, we decided to investigate whether cardanol, a phenolic CNSL component, could serve as a scaffold for improved compounds with concomitant anti-amyloid and antioxidant activities. Ten new derivatives, carrying the intact phenolic function and an aminomethyl functionality, were synthesized and first tested for their inhibitory potencies towards AChE and butyrylcholinesterase (BChE). 5 and 11 were found to inhibit human BChE at a single-digit micromolar concentration. Transmission electron microscopy revealed the potential of five derivatives to modulate A beta aggregation, including 5 and 11. In HORAC assays, 5 and 11 performed similarly to standard antioxidant ferulic acid as hydroxyl scavenging agents. Furthermore, in in vitro studies in neuronal cell cultures, 5 and 11 were found to effectively inhibit reactive oxygen species production at a 10 mu M concentration. They also showed a favorable initial ADME/Tox profile. Overall, these results suggest that CNSL is a promising raw material for the development of potential disease-modifying treatments for AD. |
| Databáze: | OpenAIRE |
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