TY  - JOUR
AU  - Bolognesi, Maria Laura
AU  - Ai Tran, Hoang Ngoc
AU  - Staderini, Matteo
AU  - Monaco, Alessandra
AU  - López-Cobeñas, Alberto
AU  - Bongarzone, Salvatore
AU  - Biarnés, Xevi
AU  - López-Alvarado, Pilar
AU  - Cabezas, Nieves
AU  - Caramelli, Maria
AU  - Carloni, Paolo
AU  - Menéndez, J. Carlos
AU  - Legname, Giuseppe
TI  - Discovery of a Class of Diketopiperazines as Antiprion Compounds
JO  - ChemMedChem
VL  - 5
IS  - 8
SN  - 1860-7179
CY  - Weinheim [u.a.]
PB  - Wiley-VCH
M1  - FZJ-2015-03575
SP  - 1324 - 1334
PY  - 2010
AB  - 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
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000281061300017
DO  - DOI:10.1002/cmdc.201000133
UR  - https://juser.fz-juelich.de/record/201270
ER  -