{"title":"Synthesis, structural characterization and study of antioxidant and anti-PrPSc properties of flavonoids and their rhenium(I)–tricarbonyl complexes","authors":"Pigi Glykofridi, Vassiliki-Eleni Tziouri, Konstantinos Xanthopoulos, Maria-Eirini Vlachou, Susana Correia, Anna-Lisa Fischer, Katrin Thüne, Antonios Hatzidimitriou, Inga Zerr, Matthias Schmitz, Theodoros Sklaviadis, Dimitra Hadjipavlou-Litina, Dionysia Papagiannopoulou","doi":"10.1007/s00775-022-01986-9","DOIUrl":null,"url":null,"abstract":"<div><p>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<sub>2</sub>O<sub>2</sub>/NaOH. The rhenium–tricarbonyl complexes of the type <i>fac</i>-[Re(CO)<sub>3</sub>(Fl)(sol)] were synthesized by reacting the precursor <i>fac</i>-[Re(CO)<sub>3</sub>(sol)<sub>3</sub>]<sup>+</sup> 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<sup>Sc</sup>, 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.</p><h3>Graphical abstract</h3>\n <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\n </div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"28 2","pages":"235 - 247"},"PeriodicalIF":2.7000,"publicationDate":"2023-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00775-022-01986-9.pdf","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JBIC Journal of Biological Inorganic Chemistry","FirstCategoryId":"1","ListUrlMain":"https://link.springer.com/article/10.1007/s00775-022-01986-9","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 1
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 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.
期刊介绍:
Biological inorganic chemistry is a growing field of science that embraces the principles of biology and inorganic chemistry and impacts other fields ranging from medicine to the environment. JBIC (Journal of Biological Inorganic Chemistry) seeks to promote this field internationally. The Journal is primarily concerned with advances in understanding the role of metal ions within a biological matrix—be it a protein, DNA/RNA, or a cell, as well as appropriate model studies. Manuscripts describing high-quality original research on the above topics in English are invited for submission to this Journal. The Journal publishes original articles, minireviews, and commentaries on debated issues.