Bibliographic Details
| Title: |
Derivatives of Tenuazonic Acid as Potential New Multi-Target Anti-Alzheimer’s Disease Agents |
| Authors: |
Viviana Poliseno, Sílvia Chaves, Leonardo Brunetti, Fulvio Loiodice, Antonio Carrieri, Antonio Laghezza, Paolo Tortorella, João D. Magalhães, Sandra M. Cardoso, M. Amélia Santos, Luca Piemontese |
| Source: |
Biomolecules, Vol 11, Iss 1, p 111 (2021) |
| Publisher Information: |
MDPI AG, 2021. |
| Publication Year: |
2021 |
| Collection: |
LCC:Microbiology |
| Subject Terms: |
Alzheimer’s disease, tenuazonic acid, donepezil, neurodegenerative, metal chelation, multifunctional drugs, Microbiology, QR1-502 |
| More Details: |
Alzheimer’s disease (AD) is generally recognized as a multifactorial neurodegenerative pathology with an increasing impact on society. Tenuazonic acid (TA) is a natural compound that was recently identified as a potential multitarget ligand with anti-cholinesterase, anti-amyloidogenic and antioxidant activities. Using its structure as a chemical scaffold, we synthesized and evaluated new derivatives (1–5), including tenuazonic-donepezil (TA-DNP) hybrids (4 and 5) due to the clinical importance of the anti-AD drug donepezil. These novel compounds all achieved activity in the micromolar range towards all selected targets and demonstrated to be potentially orally absorbed. Moreover, a selected compound (1) was further investigated as a chelating agent towards copper (II), zinc (II) and iron (III) and showed good chelating ability (pFe = 16.6, pCu = 11.6, pZn = 6.0 at pH 7.4). Therefore, the TA motif can be considered an interesting building block in the search for innovative multi-functional anti-neurodegenerative drugs, as exemplified by hybrid 5, a promising non-cytotoxic lead compound adequate for the early stages of AD, and capable of ameliorating the oxidative status of SH-SY5Y human neuroblastoma cells. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2218-273X |
| Relation: |
https://www.mdpi.com/2218-273X/11/1/111; https://doaj.org/toc/2218-273X |
| DOI: |
10.3390/biom11010111 |
| Access URL: |
https://doaj.org/article/a3c4a1415d71427290b1e8bfee5412bc |
| Accession Number: |
edsdoj.3c4a1415d71427290b1e8bfee5412bc |
| Database: |
Directory of Open Access Journals |
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