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Online ISSN: 1860-7187
June 15, 2010
VIP: Discovery of a Class of Diketopiperazines as Antiprion Compounds
Maria Laura Bolognesi,* Hoang Ngoc Ai Tran, Matteo Staderini, Alessandra Monaco, Alberto López-Cobeñas, Salvatore Bongarzone, Xevi Biarnés, Pilar López-Alvarado, Nieves Cabezas, Maria Caramelli, Paolo Carloni, J. Carlos Menéndez, and Giuseppe Legname
Transmissible spongiform encephalopathies (TSEs, also known as prion diseases) are infectious neurodegenerative diseases for which pharmacological treatment is not yet available. Bolognesi et al. have identified a bifunctional diketopiperazine (DKP) derivative that shows promising activity against prion replication in ScGT1 cells while maintaining low cytotoxicity. Molecular modeling studies led the authors to suggest the planarity of the DKP derivative as a key determinant for its efficacy; it is proposed to interact directly with recombinant prion protein, thus preventing its conversion to the misfolded pathogenic form. Compounds based on this scaffold could serve as additional promising leads for the eventual development of drugs to combat TSEs.
Received March 29, 2010; published online June 10, 2010, DOI: 10.1002/cmdc.201000133.