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  3. Novel anti-Alzheimer phenol-lipoyl hybrids: Synthesis, physico-chemical characterization, and biological evaluation

Novel anti-Alzheimer phenol-lipoyl hybrids: Synthesis, physico-chemical characterization, and biological evaluation

  • Eur J Med Chem. 2020 Jan 15;186:111880. doi: 10.1016/j.ejmech.2019.111880.
Aikaterini Pagoni 1,  Lisa Marinelli 2,  Antonio Di Stefano 2,  Michele Ciulla 2,  Hasan Turkez 3,  Adil Mardinoglu 4,  Stamatia Vassiliou 5,  Ivana Cacciatore 6
Affiliations

Affiliations

  • 1 Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Athens, Greece.
  • 2 Department of Pharmacy, "G. D'Annunzio" University of Chieti-Pescara, 66100, Chieti Scalo, CH, Italy.
  • 3 Department of Molecular Biology and Genetics, Faculty of Science, Erzurum Technical University, Erzurum, Turkey.
  • 4 Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, SE-17121, Sweden; Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, SE1 9RT, United Kingdom.
  • 5 Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: svassiliou@chem.uoa.gr.
  • 6 Department of Pharmacy, "G. D'Annunzio" University of Chieti-Pescara, 66100, Chieti Scalo, CH, Italy. Electronic address: ivana.cacciatore@unich.it.
PMID: 31753513 DOI: 10.1016/j.ejmech.2019.111880
Abstract

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.

Keywords

Alzheimer’s disease; Hybrid; Lipoic acid; Polyphenol.

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