Synthesis, structural characterization and study of antioxidant and anti-PrPSc properties of flavonoids and their rhenium(I)–tricarbonyl complexes

Abstract

Abstract 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 H 2 O 2 /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, PrP Sc , 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. Graphical abstract