- Titel
- Modulation of γ-Secretase Activity by a Carborane-Based Flurbiprofen Analogue
- Zitierfähige Url:
- https://nbn-resolving.org/urn:nbn:de:bsz:15-qucosa2-852948
- Quellenangabe
- Molecules
Erscheinungsjahr: 2021
Jahrgang: 26
Heft: 10
E-ISSN: 1420-3049
Artikelnummer: 2843 - Erstveröffentlichung
- 2021
- Abstract (EN)
- All over the world, societies are facing rapidly aging populations combined with a growing number of patients suffering from Alzheimer’s disease (AD). One focus in pharmaceutical research to address this issue is on the reduction of the longer amyloid-β (Aβ) fragments in the brain by modulation of γ-secretase, a membrane-bound protease. R-Flurbiprofen (tarenflurbil) was studied in this regard but failed to show significant improvement in AD patients in a phase 3 clinical trial. This was mainly attributed to its low ability to cross the blood–brain barrier (BBB). Here, we present the synthesis and in vitro evaluation of a racemic meta-carborane analogue of flurbiprofen. By introducing the carborane moiety, the hydrophobicity could be shifted into a more favourable range for the penetration of the blood–brain barrier, evident by a logD7.4 value of 2.0. Furthermore, our analogue retained γ-secretase modulator activity in comparison to racemic flurbiprofen in a cell-based assay. These findings demonstrate the potential of carboranes as phenyl mimetics also in AD research.
- Andere Ausgabe
- Link zur Erstveröffentlichung
Link: https://doi.org/10.3390/molecules26102843 - Freie Schlagwörter (EN)
- Alzheimer; carborane; flurbiprofen; γ-secretase modulator (GSM); small molecule; amyloid-β (Aβ) peptide; phenyl mimetic
- Klassifikation (DDC)
- 540
- Verlag
- MDPI, Basel
- Version / Begutachtungsstatus
- publizierte Version / Verlagsversion
- URN Qucosa
- urn:nbn:de:bsz:15-qucosa2-852948
- Veröffentlichungsdatum Qucosa
- 05.05.2023
- Dokumenttyp
- Artikel
- Sprache des Dokumentes
- Englisch
- Lizenz / Rechtehinweis
CC BY 4.0