| Autor: |
Di Santo R; Dipartimento di Chimica e Tecnologie del Farmaco, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza Università di Roma, P.le A. Moro 5, I-00185 Roma, Italy. roberto.disanto@uniroma1.it, Costi R, Cuzzucoli Crucitti G, Pescatori L, Rosi F, Scipione L, Celona D, Vertechy M, Ghirardi O, Piovesan P, Marzi M, Caccia S, Guiso G, Giorgi F, Minetti P |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 2012 Oct 11; Vol. 55 (19), pp. 8538-48. Date of Electronic Publication: 2012 Oct 01. |
| DOI: |
10.1021/jm301105m |
| Abstrakt: |
Dyes like CR are able to inhibit the aggregation of Aβ fibrils. Thus, a screening of a series of dyes including ABBB (1) was performed. Its main component 2 tested in an in vitro assay (i.e., ThT assay) showed good potency at inhibiting fibrils association. Congeners 4-9 have been designed and synthesized as inhibitors of Aβ aggregation. A number of these newly synthesized compounds have been found to be active in the ThT assay with IC(50) of 1-57.4 μM. The most potent compound of this series, 4k, showed micromolar activity in this test. Another potent derivative 4q (IC(50) = 5.6 μM) rapidly crossed the blood-brain barrier, achieving whole brain concentrations higher than in plasma. So 4q could be developed to find novel potent antiaggregating βA agents useful in Alzheimer disease as well as other neurological diseases characterized by deposits of amyloid aggregates. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
