Publication: Synthesis, biological evaluation and molecular modeling study of novel tacrine-carbazole hybrids as potential multifunctional agents for the treatment of Alzheimer's disease
2
Issued Date
2014-03-21
Resource Type
ISSN
17683254
02235234
02235234
Other identifier(s)
2-s2.0-84893731184
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Mahidol University
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SCOPUS
Bibliographic Citation
European Journal of Medicinal Chemistry. Vol.75, (2014), 21-30
Suggested Citation
Supatra Thiratmatrakul, Chavi Yenjai, Pornthip Waiwut, Opa Vajragupta, Prasert Reubroycharoen, Michihisa Tohda, Chantana Boonyarat Synthesis, biological evaluation and molecular modeling study of novel tacrine-carbazole hybrids as potential multifunctional agents for the treatment of Alzheimer's disease. European Journal of Medicinal Chemistry. Vol.75, (2014), 21-30. doi:10.1016/j.ejmech.2014.01.020 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/33625
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Title
Synthesis, biological evaluation and molecular modeling study of novel tacrine-carbazole hybrids as potential multifunctional agents for the treatment of Alzheimer's disease
Abstract
New tacrine-carbazole hybrids were developed as potential multifunctional anti-Alzheimer agents for their cholinesterase inhibitory and radical scavenging activities. The developed compounds showed high inhibitory activity on acetylcholinesterase (AChE) with IC50values ranging from 0.48 to 1.03 μM and exhibited good inhibition selectivity against AChE over butyrylcholinesterase (BuChE). Molecular modeling studies revealed that these tacrine-carbazole hybrids interacted simultaneously with the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. The derivatives containing methoxy group showed potent ABTS radical scavenging activity. Considering their neuroprotection, our results indicate that these derivatives can reduce neuronal death induced by oxidative stress and β-amyloid (Aβ). Moreover, S1, the highest potency for both radical scavenging and AChE inhibitory activity, exhibited an ability to improve both short-term and long-term memory deficit in mice induced by scopolamine. Overall, tacrine-carbazole derivatives can be considered as a candidate with potential impact for further pharmacological development in Alzheimer's therapy. © 2014 Elsevier Masson SAS. All rights reserved.