TY  - JOUR
AU  - Glykofridi, Pigi
AU  - Tziouri, Vassiliki-Eleni
AU  - Xanthopoulos, Konstantinos
AU  - Vlachou, Maria-Eirini
AU  - Silva-Correia, Susana
AU  - Fischer, Anna-Lisa
AU  - Thüne, Katrin
AU  - Hatzidimitriou, Antonios
AU  - Zerr, Inga
AU  - Schmitz, Matthias
AU  - Sklaviadis, Theodoros
AU  - Hadjipavlou-Litina, Dimitra
AU  - Papagiannopoulou, Dionysia
TI  - Synthesis, structural characterization and study of antioxidant and anti-PrPSc properties of flavonoids and their rhenium(I)-tricarbonyl complexes.
JO  - Journal of biological inorganic chemistry
VL  - 28
IS  - 2
SN  - 0949-8257
CY  - New York
PB  - Springer
M1  - DZNE-2023-00335
SP  - 235 - 247
PY  - 2023
N1  - CC BY
AB  - This study aims at the synthesis and initial biological evaluation of novel rhenium-tricarbonyl complexes of 3,3',4',5,7-pentahydroxyflavone (quercetin), 3,7,4΄-trihydroxyflavone (resokaempferol), 5,7-dihydroxyflavone (chrysin) and 4΄,5,7-trihydroxyflavonone (naringenin) as neuroprotective and anti-PrP agents. Resokaempferol was synthesized from 2,2΄,4-trihydroxychalcone by H2O2/NaOH. The rhenium-tricarbonyl complexes of the type fac-[Re(CO)3(Fl)(sol)] were synthesized by reacting the precursor fac-[Re(CO)3(sol)3]+ with an equimolar amount of the flavonoids (Fl) quercetin, resokaempferol, chrysin and naringenin and the solvent (sol) was methanol or water. The respective Re-flavonoid complexes were purified by semi-preparative HPLC and characterized by spectroscopic methods. Furthermore, the structure of Re-chrysin was elucidated by X-ray crystallography. Initial screening of the neuroprotective properties of these compounds included the in vitro assessment of the antioxidant properties by the DPPH assay as well as the anti-lipid peroxidation of linoleic acid in the presence of AAPH and their ability to inhibit soybean lipoxygenase. From the above studies, it was concluded that the complexes' properties are mainly correlated with the structural characteristics and the presence of the flavonoids. The flavonoids and their respective Re-complexes were also tested in vitro for their ability to inhibit the formation and aggregation of the amyloid-like abnormal prion protein, PrPSc, by employing the real-time quaking-induced conversion assay with recombinant PrP seeded with cerebrospinal fluid from patients with Creutzfeldt-Jakob disease. All the compounds blocked de novo abnormal PrP formation and aggregation.
KW  - Flavonoids: chemistry
KW  - Humans
KW  - Antioxidants: pharmacology
KW  - Rhenium: chemistry
KW  - Quercetin
KW  - Hydrogen Peroxide
KW  - Crystallography, X-Ray
KW  - Flavonoids: pharmacology
KW  - PrPSc Proteins: drug effects
KW  - PrPSc Proteins: metabolism
KW  - Organometallic Compounds: chemistry
KW  - Organometallic Compounds: pharmacology
KW  - Flavonoids (NLM Chemicals)
KW  - Anti-oxidant (Other)
KW  - Flavonoids (Other)
KW  - Lipid peroxidation (Other)
KW  - Lipoxygenase (Other)
KW  - Prion diseases (Other)
KW  - Rhenium complexes (Other)
KW  - Antioxidants (NLM Chemicals)
KW  - Rhenium (NLM Chemicals)
KW  - Quercetin (NLM Chemicals)
KW  - Hydrogen Peroxide (NLM Chemicals)
KW  - 5-deoxykaempferol (NLM Chemicals)
KW  - chrysin (NLM Chemicals)
KW  - naringenin (NLM Chemicals)
KW  - PrPSc Proteins (NLM Chemicals)
KW  - Organometallic Compounds (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:36695886
C2  - pmc:PMC9981504
DO  - DOI:10.1007/s00775-022-01986-9
UR  - https://pub.dzne.de/record/256473
ER  -