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Molecules 2017, 22(8), 1265; doi:10.3390/molecules22081265

Development of 2-Methoxyhuprine as Novel Lead for Alzheimer’s Disease Therapy

1
Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic
2
National Institute of Mental Health, Topolova 748, 250 67 Klecany, Czech Republic
3
Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, University of Defence in Brno, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic
4
Department of Organic and Biorganic Chemistry, Faculty of Pharmacy in Hradec Kralove, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic
5
Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanskeho 62, 500 03 Hradec Kralove, Czech Republic
*
Author to whom correspondence should be addressed.
Received: 3 July 2017 / Revised: 21 July 2017 / Accepted: 22 July 2017 / Published: 28 July 2017
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Abstract

Tacrine (THA), the first clinically effective acetylcholinesterase (AChE) inhibitor and the first approved drug for the treatment of Alzheimer’s disease (AD), was withdrawn from the market due to its side effects, particularly its hepatotoxicity. Nowadays, THA serves as a valuable scaffold for the design of novel agents potentially applicable for AD treatment. One such compound, namely 7-methoxytacrine (7-MEOTA), exhibits an intriguing profile, having suppressed hepatotoxicity and concomitantly retaining AChE inhibition properties. Another interesting class of AChE inhibitors represents Huprines, designed by merging two fragments of the known AChE inhibitors—THA and (−)-huperzine A. Several members of this compound family are more potent human AChE inhibitors than the parent compounds. The most promising are so-called huprines X and Y. Here, we report the design, synthesis, biological evaluation, and in silico studies of 2-methoxyhuprine that amalgamates structural features of 7-MEOTA and huprine Y in one molecule. View Full-Text
Keywords: acetylcholinesterase; Alzheimer’s disease; butyrylcholinesterase; tacrine; 7-MEOTA; huprine Y; 2-methoxyhuprine acetylcholinesterase; Alzheimer’s disease; butyrylcholinesterase; tacrine; 7-MEOTA; huprine Y; 2-methoxyhuprine
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Mezeiova, E.; Korabecny, J.; Sepsova, V.; Hrabinova, M.; Jost, P.; Muckova, L.; Kucera, T.; Dolezal, R.; Misik, J.; Spilovska, K.; Pham, N.L.; Pokrievkova, L.; Roh, J.; Jun, D.; Soukup, O.; Kaping, D.; Kuca, K. Development of 2-Methoxyhuprine as Novel Lead for Alzheimer’s Disease Therapy. Molecules 2017, 22, 1265.

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