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@ARTICLE{Bolognesi:201270,
author = {Bolognesi, Maria Laura and Ai Tran, Hoang Ngoc and
Staderini, Matteo and Monaco, Alessandra and
López-Cobeñas, Alberto and Bongarzone, Salvatore and
Biarnés, Xevi and López-Alvarado, Pilar and Cabezas,
Nieves and Caramelli, Maria and Carloni, Paolo and
Menéndez, J. Carlos and Legname, Giuseppe},
title = {{D}iscovery of a {C}lass of {D}iketopiperazines as
{A}ntiprion {C}ompounds},
journal = {ChemMedChem},
volume = {5},
number = {8},
issn = {1860-7179},
address = {Weinheim [u.a.]},
publisher = {Wiley-VCH},
reportid = {FZJ-2015-03575},
pages = {1324 - 1334},
year = {2010},
abstract = {Prion diseases are fatal neurodegenerative and infectious
disorders for which effective pharmacological tools are not
yet available. This unmet challenge and the recently
proposed interplay between prion diseases and Alzheimer's
have led to a more urgent demand for new antiprion agents.
Herein, we report the identification of a novel bifunctional
diketopiperazine (DKP) derivative 1 d, which exhibits
activity in the low micromolar range against prion
replication in ScGT1 cells, while showing low cytotoxicity.
Supported by properly addressed molecular modeling studies,
we hypothesized that a planar conformation is the major
determinant for activity in this class of compounds.
Moreover, studies aimed at assessing the mechanism-of-action
at the molecular level showed that 1 d might interact
directly with recombinant prion protein (recPrP) to prevent
its conversion to the pathogenic misfolded prion protein
(PrPSc)-like form. This investigation suggests that DKP
based antiprion compounds can serve as a promising lead
scaffold in developing new drugs to combat prion diseases},
cin = {GRS / IAS-5},
ddc = {540},
cid = {I:(DE-Juel1)GRS-20100316 / I:(DE-Juel1)IAS-5-20120330},
pnm = {899 - ohne Topic (POF2-899)},
pid = {G:(DE-HGF)POF2-899},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000281061300017},
doi = {10.1002/cmdc.201000133},
url = {https://juser.fz-juelich.de/record/201270},
}