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  • Novel multi-target-directed ligands aiming at symptoms and causes of Alzheimer's disease [Elektronski vir]
    Więckowska, Anna ...
    Alzheimer's disease (AD) is a major public health problem, which is due to its increasing prevalence and lack of effective therapy or diagnostics. Complexity of AD pathomechanism requires complex ... treatment e.g. multifunctional ligands targeting both causes and symptoms of the disease. Here, we present new multi-target-directed ligands combining pharmacophore fragments that provide blockade of serotonin 5-HT6 receptors, acetyl/butyrylcholinesterase inhibition, and amyloid beta anti-aggregation activity. Compound 12 has displayed balanced activity as an antagonist of 5-HT6 receptors (Ki = 18 nM) and non-competitive inhibitor of cholinesterases (IC50hAChE = 14 nM, IC50eqBuChE = 22 nM). In further in vitro studies, compound 12 has shown amyloid beta anti-aggregation activity (IC50 = 1.27 microM) and ability to permeate through the blood-brain barrier. The presented findings may provide and excellent starting point for further studies and facilitate efforts to develop new effective anti-AD therapy.
    Source: ACS chemical neuroscience. - ISSN 1948-7193 (Vol. 9, iss. 5, 2018, str. 1195-1214)
    Type of material - e-article
    Publish date - 2018
    Language - english
    COBISS.SI-ID - 4470641

    Link(s):

    https://pubs.acs.org/doi/10.1021/acschemneuro.8b00024
    DOI

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