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  • Design, synthesis, and biological evaluation of 2-(benzylamino-2-hydroxyalkyl)isoindoline-1,3-diones derivatives as potential disease-modifying multifunctional anti-Alzheimer agents [Elektronski vir]
    Panek, Dawid ...
    The complex nature of Alzheimer's disease calls for multidirectional treatment. Consequently, the search for multi-target-directed ligands may lead to potential drug candidates. The aim of the ... present study is to seek multifunctional compounds with expected activity against disease-modifying and symptomatic targets. A series of 15 drug-like various substituted derivatives of 2-(benzylamino-2-hydroxyalkyl)isoindoline-1,3-diones was designed by modification of cholinesterase inhibitors toward beta-secretase inhibition. All target compounds have been synthesized and tested against eel acetylcholinesterase (eeAChE), equine serum butyrylcholinesterase (eqBuChE), human %-secretase (hBACE-1), and beta-amyloid (A beta-aggregation). The most promising compound, 12 (2-(5-(benzylamino)-4-hydroxypentyl)isoindoline-1,3-dione), displayed inhibitory potency against eeAChE (IC50 = 3.33 microM), hBACE-1 (43.7% at 50 microM), and A beta-aggregation (24.9% at 10 microM). Molecular modeling studies have revealed possible interaction of compound 12 with the active sites of both enzymes acetylcholinesterase and beta-secretase. In conclusion: modifications of acetylcholinesterase inhibitors led to the discovery of a multipotent anti-Alzheimer's agent, with moderate and balanced potency, capable of inhibiting acetylcholinesterase, a symptomatic target, and disease-modifying targets: beta-secretase and A beta-aggregation.
    Source: Molecules [Elektronski vir]. - ISSN 1420-3049 (Vol. 23, iss. 2, 2018, str. 1-15)
    Type of material - e-article
    Publish date - 2018
    Language - english
    COBISS.SI-ID - 4473713

    Link(s):

    http://www.mdpi.com/1420-3049/23/2/347

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