AI Article Synopsis
- Tacrine was the first effective treatment for Alzheimer's but was pulled from the market due to harmful side effects like liver damage.
- A new compound, 7-methoxytacrine, shows promise as it maintains AChE inhibition without the severe side effects associated with tacrine.
- Researchers are now focusing on 2-methoxyhuprine, a compound that combines elements of both 7-MEOTA and another potent inhibitor, huprine Y, in hopes of creating a safer and more effective treatment for Alzheimer's disease.
Article 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acetylcholinesterase (AChE) inhibitor and the first approved drug for the treatment of Alzheimer's disease (AD), was withdrawn from the market due to its side effects, particularly its hepatotoxicity.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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6152224 | PMC |
| http://dx.doi.org/10.3390/molecules22081265 | DOI Listing |
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