Donepezil Derivatives Targeting Amyloid-β Cascade in Alzheimer's Disease

Current Alzheimer Research
Eva MezeiovaJan Korabecny

Abstract

Alzheimer's Disease (AD) is a neurodegenerative disorder with an increasing impact on society. Because currently available therapy has only a short-term effect, a huge number of novel compounds are developed every year exploiting knowledge of the various aspects of AD pathophysiology. To better address the pathological complexity of AD, one of the most extensively pursued strategies by medicinal chemists is based on Multi-target-directed Ligands (MTDLs). Donepezil is one of the currently approved drugs for AD therapy acting as an acetylcholinesterase inhibitor. In this review, we have made an extensive literature survey focusing on donepezil-derived MTDL hybrids primarily targeting on different levels cholinesterases and amyloid beta (Aβ) peptide. The targeting includes direct interaction of the compounds with Aβ, AChE-induced Aβ aggregation, inhibition of BACE-1 enzyme, and modulation of biometal balance thus impeding Aβ assembly.

References

Apr 10, 1992·Science·J A Hardy, G A Higgins
Jul 1, 1990·The British Journal of Psychiatry : the Journal of Mental Science·A BurnsR Levy
Jun 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·C L MastersK Beyreuther
Apr 1, 1984·The Biochemical Journal·B Halliwell, J M Gutteridge
Nov 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·A E RoherM J Ball
Jan 16, 1998·American Journal of Health-system Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists·E Y Shintani, K M Uchida
Jul 17, 1998·Journal of the Neurological Sciences·M A LovellW R Markesbery
Jan 19, 2000·Current Medicinal Chemistry·H SugimotoY Kawakami
Aug 6, 2000·British Journal of Pharmacology·C RoutledgeD N Middlemiss
Sep 7, 2001·Journal of Medicinal Chemistry·C BrühlmannA Carotti
Jan 16, 2003·Biochemical Pharmacology·Manuela BartoliniVincenza Andrisano
Mar 1, 2003·Journal of Natural Products·Chihiro ItoHiroshi Furukawa
Mar 20, 2003·Bioorganic & Medicinal Chemistry Letters·Katalin Prokai-TatraiLaszlo Prokai
Apr 10, 2003·Experimental Neurology·Anna M CanudasMercè Pallàs
Aug 21, 2003·Progress in Neurobiology·Paul R TurnerWickliffe C Abraham
Aug 23, 2003·Journal of Natural Products·Yi-Ming ChiangYoshiyasu Fukuyama
Dec 31, 2003·Neurotoxicology·Peter RiedererEdna Grünblatt
Apr 24, 2004·Annals of the New York Academy of Sciences·Xudong HuangJack T Rogers
Nov 3, 2004·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·S K SonkusareP Ramarao
Dec 14, 2004·Journal of Medicinal Chemistry·Shawn J StachelJoseph P Vacca
Oct 19, 2005·Bioorganic & Medicinal Chemistry·D AlonsoA Martínez
Nov 25, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Rodney A VelliquetteRobert Vassar
Jan 20, 2006·The European Journal of Neuroscience·Masuo OhnoJohn F Disterhoft
Feb 16, 2006·Current Medicinal Chemistry·D Muñoz-Torrero, P Camps
Jun 7, 2007·Nature Reviews. Neuroscience·Frank M LaFerlaSalvatore Oddo

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Citations

Oct 1, 2019·Physical Chemistry Chemical Physics : PCCP·Shivani Gupta, Ashok Kumar Dasmahapatra
Nov 16, 2019·Current Alzheimer Research·Ondrej Soukup, Jan Korabecny
Jul 28, 2020·ChemMedChem·Rosaria PeroneMaria Laura Bolognesi
Feb 27, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sílvia ChavesM Amélia Santos
May 26, 2020·Trends in Pharmacological Sciences·Ondrej BenekOndrej Soukup
Mar 23, 2021·Journal of Alzheimer's Disease : JAD·Roger GaudreaultCharles Ramassamy
Jul 25, 2020·Journal of Medicinal Chemistry·F Javier Pérez-ArealesDiego Muñoz-Torrero

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