Multitarget Drug Design Strategy: Quinone-Tacrine Hybrids Designed To Block Amyloid-beta Aggregation and To Exert Anticholinesterase and Antioxidant Effects (Articolo in rivista)

Type

• Prodotto della ricerca (Classe)
• Articolo in rivista (Classe)

Label

• Multitarget Drug Design Strategy: Quinone-Tacrine Hybrids Designed To Block Amyloid-beta Aggregation and To Exert Anticholinesterase and Antioxidant Effects (Articolo in rivista) (literal)

Anno

• 2014-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

• 10.1021/jm5010804 (literal)

Alternative label

• Nepovímová, Eugenie; Uliassi, Elisa; Korábecný, Jan; Peña-Altamira, Luis Emiliano; Samez, Sarah; Pesaresi, Alessandro; Garcia, Gregory E.; Bartolini, Manuela; Andrisano, Vincenza; Bergamini, Christian; Fato, Romana; Lamba, Doriano; Roberti, Marinella; Kuca, Kamil; Monti, Barbara; Bolognesi, M. L. (2014)
  Multitarget Drug Design Strategy: Quinone-Tacrine Hybrids Designed To Block Amyloid-beta Aggregation and To Exert Anticholinesterase and Antioxidant Effects
  in Journal of medicinal chemistry; American Chemical Society, Washington, DC (Stati Uniti d'America)
  (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

• Nepovímová, Eugenie; Uliassi, Elisa; Korábecný, Jan; Peña-Altamira, Luis Emiliano; Samez, Sarah; Pesaresi, Alessandro; Garcia, Gregory E.; Bartolini, Manuela; Andrisano, Vincenza; Bergamini, Christian; Fato, Romana; Lamba, Doriano; Roberti, Marinella; Kuca, Kamil; Monti, Barbara; Bolognesi, M. L. (literal)

Pagina inizio

• 8576 (literal)

Pagina fine

• 8589 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url

• http://www.scopus.com/record/display.url?eid=2-s2.0-84908375105&origin=inward (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

• 57 (literal)

Rivista

• Journal of medicinal chemistry (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali

• 14 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo

• 20 (literal)

Note

• ubMe (literal)
• ISI Web of Science (WOS) (literal)
• Scopu (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

• Alma Mater Studiorum Universita di Bologna; Univerzita obrany v Brne; Faculty Hospital at Hradec Kralove; Charles University in Prague; Consiglio Nazionale delle Ricerche; Universita degli Studi di Trieste; US Army Medical Research Institute of Chemical Defense (literal)

Titolo

• Multitarget Drug Design Strategy: Quinone-Tacrine Hybrids Designed To Block Amyloid-beta Aggregation and To Exert Anticholinesterase and Antioxidant Effects (literal)

Abstract

• We report the identification of multitarget anti-Alzheimer compounds designed by combining a naphthoquinone function and a tacrine fragment. In vitro, 15 compounds displayed excellent acetylcholinesterase (AChE) inhibitory potencies and interesting capabilities to block amyloid-beta (Abeta) aggregation. The X-ray analysis of one of those compounds in complex with AChE allowed rationalizing the outstanding activity data (IC50 = 0.72 nM). Two of the compounds showed negligible toxicity inimmortalized mouse cortical neurons Neuro2A and primary rat cerebellar granule neurons. However, only one of them was less hepatotoxic than tacrine in HepG2 cells. In T67 cells, both compounds showed antioxidant activity, following NQO1 induction. Furthermore, in Neuro2A, they were able to completely revert the decrease in viability induced by Abeta. Importantly, they crossed the blood-brain barrier, as demonstrated in ex vivo experiments with rats. When ex vivo results were combined with in vitro studies, these two compounds emerged to be promising multitarget lead candidates worthy of further pursuit. (literal)

Editore

• American Chemical Society (Editore)

Prodotto di

• Institute of Crystallography (IC) (Istituto)
• Studi strutturali e funzionali di proteine di interesse biomedico e biotecnologico (PM.P01.023.001) (Modulo)

Autore CNR

• DORIANO LAMBA (Unità di personale interno)
• ALESSANDRO PESARESI (Unità di personale interno)

Insieme di parole chiave

• Keywords of "Multitarget Drug Design Strategy: Quinone-Tacrine Hybrids Designed To Block Amyloid-beta Aggregation and To Exert Anticholinesterase and Antioxidant Effects" (Insieme di parole chiave)

Incoming links:

Prodotto

• Institute of Crystallography (IC) (Istituto)
• Studi strutturali e funzionali di proteine di interesse biomedico e biotecnologico (PM.P01.023.001) (Modulo)

Autore CNR di

• DORIANO LAMBA (Unità di personale interno)
• ALESSANDRO PESARESI (Unità di personale interno)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi

• Journal of medicinal chemistry (Rivista)

Editore di

• American Chemical Society (Editore)

Insieme di parole chiave di

• Keywords of "Multitarget Drug Design Strategy: Quinone-Tacrine Hybrids Designed To Block Amyloid-beta Aggregation and To Exert Anticholinesterase and Antioxidant Effects" (Insieme di parole chiave)