TY - JOUR
T1 - Novel anti-Alzheimer phenol-lipoyl hybrids
T2 - Synthesis, physico-chemical characterization, and biological evaluation
AU - Pagoni, Aikaterini
AU - Marinelli, Lisa
AU - Di Stefano, Antonio
AU - Ciulla, Michele
AU - Turkez, Hasan
AU - Mardinoglu, Adil
AU - Vassiliou, Stamatia
AU - Cacciatore, Ivana
PY - 2020/1/15
Y1 - 2020/1/15
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Hybrid
KW - Lipoic acid
KW - Polyphenol
UR - http://www.scopus.com/inward/record.url?scp=85075479242&partnerID=8YFLogxK
U2 - 10.1016/j.ejmech.2019.111880
DO - 10.1016/j.ejmech.2019.111880
M3 - Article
C2 - 31753513
AN - SCOPUS:85075479242
SN - 0223-5234
VL - 186
JO - EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
JF - EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
M1 - 111880
ER -
