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We identified (<jats:italic>E<\/jats:italic>)\u20103\u2010(hydroxy\u20103\u2010methoxyphenyl)\u2010<jats:italic>N<\/jats:italic>\u2010{8[(7\u2010methoxy\u20101,2,3,4\u2010tetrahydroacridin\u20109\u2010yl)amino]octyl}\u2010<jats:italic>N<\/jats:italic>\u2010[2\u2010(naphthalen\u20102\u2010ylamino)2\u2010oxoethyl]acrylamide (TFAH <jats:bold>10\u2009n<\/jats:bold>) as a particularly interesting multipotent compound that shows moderate and completely selective inhibition of human butyrylcholinesterase (IC<jats:sub>50<\/jats:sub>=68.2\u2005n<jats:sc>M<\/jats:sc>), strong antioxidant activity (4.29\u2005equiv trolox in an oxygen radical absorbance capacity (ORAC) assay), and good \u03b2\u2010amyloid (A\u03b2) anti\u2010aggregation properties (65.6\u2009% at 1:1 ratio); moreover, it is able to permeate central nervous system (CNS) tissues, as determined by PAMPA\u2010BBB assay. Notably, even when tested at very high concentrations, TFAH <jats:bold>10\u2009n<\/jats:bold> easily surpasses the other TFAHs in hepatotoxicity profiling (59.4\u2009% cell viability at 1000\u2005\u03bc<jats:sc>M<\/jats:sc>), affording good neuroprotection against toxic insults such as A\u03b2<jats:sub>1\u201340<\/jats:sub>, A\u03b2<jats:sub>1\u201342<\/jats:sub>, H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>, and oligomycin\u2005A\/rotenone on SH\u2010SY5Y cells, at 1\u2005\u03bc<jats:sc>M<\/jats:sc>. The results reported herein support the development of new multipotent TFAH derivatives as potential drugs for the treatment of Alzheimer\u2032s disease.<\/jats:p>","DOI":"10.1002\/cmdc.201402409","type":"journal-article","created":{"date-parts":[[2014,12,23]],"date-time":"2014-12-23T17:16:58Z","timestamp":1419355018000},"page":"523-539","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Novel Tacrine\u2010Grafted Ugi Adducts as Multipotent Anti\u2010Alzheimer Drugs: A Synthetic Renewal in Tacrine\u2013Ferulic Acid 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