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Novel anti-Alzheimer phenol-lipoyl hybrids: Synthesis, physico-chemical characterization, and biological evaluation
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2020 (English)In: European Journal of Medicinal Chemistry, ISSN 0223-5234, E-ISSN 1768-3254, Vol. 186, article id 111880Article in journal (Refereed) Published
Abstract [en]

To date, drugs that hit a single target are inadequate for the treatment of neurodegenerative diseases, such as Alzheimer's or Parkinson's diseases. The development of multitarget ligands, able to interact with the different pathways involved in the progession of these disorders, represents a great challenge for medicinal chemists. In this context, we report here the synthesis and biological evaluation of phenol-lipoyl hybrids (SV1-13), obtained via a linking strategy, to take advantage of the synergistic effect due to the antioxidant portions and anti-amyloid properties of the single constituents present in the hybrid molecule. Biological results showed that SV5 and SV10 possessed the best protective activity against Aβ1-42 induced neurotoxicity in differentiated SH-SY5Y cells. SV9 and SV10 showed remarkable antioxidant properties due to their ability to counteract the damage caused by H2O2 in SHSY-5Y-treated cells. Hovewer, SV5, showing moderate antioxidant and good neuroprotective activities, resulted the best candidate for further experiments since it also resulted stable both simulated and plasma fluids.

Place, publisher, year, edition, pages
Elsevier Masson SAS , 2020. Vol. 186, article id 111880
Keywords [en]
Alzheimer's disease, Hybrid, Lipoic acid, Polyphenol
National Category
Basic Medicine
Identifiers
URN: urn:nbn:se:kth:diva-267830DOI: 10.1016/j.ejmech.2019.111880ISI: 000509616800027PubMedID: 31753513Scopus ID: 2-s2.0-85075479242OAI: oai:DiVA.org:kth-267830DiVA, id: diva2:1412456
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QC 20200306

Available from: 2020-03-06 Created: 2020-03-06 Last updated: 2020-03-16Bibliographically approved

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Mardinoglu, Adil

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