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Sterubin: Enantioresolution and Configurational Stability,Enantiomeric Purity in Nature,and Neuroprotective Activity in Vitro and in Vivo |
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| Authors: | Julian Hofmann Dr Shaimaa Fayez Matthias Scheiner Dr Matthias Hoffmann Dr Sabrina Oerter Dr Antje Appelt-Menzel Dr Pamela Maher Dr Tangui Maurice Prof?Dr Gerhard Bringmann Prof?Dr Michael Decker |
| Institution: | 1. Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany
These authors contributed equally.;2. Institute of Organic Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Organization of African Unity Street 1, 11566 Cairo, Egypt These authors contributed equally.;3. Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany;4. Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany MMDN, University of Montpellier, INSERM, EPHE, UMR-S1198, 34095 Montpellier, France;5. Department for Tissue Engineering and Regenerative Medicine, University Hospital Würzburg, Röntgenring 11, 97070 Würzburg, Germany;6. Department for Tissue Engineering and Regenerative Medicine, University Hospital Würzburg, Röntgenring 11, 97070 Würzburg, Germany Translational Center Regenerative Therapies (TLC-RT), Fraunhofer Institute for Silicate Research ISC, Röntgenring 11, 97070 Würzburg, Germany;7. The Salk Institute for Biological Studies, 10010 North Torrey Pines Rd., CA, 92037 La Jolla, USA;8. MMDN, University of Montpellier, INSERM, EPHE, UMR-S1198, 34095 Montpellier, France;9. Institute of Organic Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany |
| Abstract: | Alzheimer′s disease (AD) is a neurological disorder with still no preventive or curative treatment. Flavonoids are phytochemicals with potential therapeutic value. Previous studies described the flavanone sterubin isolated from the Californian plant Eriodictyon californicum as a potent neuroprotectant in several in vitro assays. Herein, the resolution of synthetic racemic sterubin ( 1 ) into its two enantiomers, (R)- 1 and (S)- 1 , is described, which has been performed on a chiral chromatographic phase, and their stereochemical assignment online by HPLC-ECD coupling. (R)- 1 and (S)- 1 showed comparable neuroprotection in vitro with no significant differences. While the pure stereoisomers were configurationally stable in methanol, fast racemization was observed in the presence of culture medium. We also established the occurrence of extracted sterubin as its pure (S)-enantiomer. Moreover, the activity of sterubin ( 1 ) was investigated for the first time in vivo, in an AD mouse model. Sterubin ( 1 ) showed a significant positive impact on short- and long-term memory at low dosages. |
| Keywords: | Alzheimer′s disease chiral resolution circular dichroism Eriodictyon californicum flavonoids sterubin |