{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hamulakova S"],"funding":["IT4Neur","NIA NIH HHS","Dually Acting Cognitive Enhancers for Palliative Treatment of Alzheimer&apos;s Disease","Long-term organization development plan of the Faculty of Military Health Sciences, University of Defence","Štúdium cytotoxickej altivity nových kumarínových derivátov modifikovaných akridínovým, takrínovým a antracénovým skeletom"],"pagination":["785-804"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8488533"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(9)"],"pubmed_abstract":["The authors report on the synthesis and biological evaluation of new compounds whose structure combines tacrine and indole moieties. Tacrine-indole heterodimers were designed to inhibit cholinesterases and β-amyloid formation, and to cross the blood-brain barrier. The most potent new acetylcholinesterase inhibitors were compounds <b>3c</b> and <b>4d</b> (IC<sub>50</sub> = 25 and 39 nM, respectively). Compound <b>3c</b> displayed considerably higher selectivity for acetylcholinesterase relative to human plasma butyrylcholinesterase in comparison to compound <b>4d</b> (selectivity index: IC<sub>50</sub> [butyrylcholinesterase]/IC<sub>50</sub> [acetylcholinesterase] = 3 and 0.6, respectively). Furthermore, compound <b>3c</b> inhibited β-amyloid-dependent amyloid nucleation in the yeast-based prion nucleation assay and displayed no dsDNA destabilizing interactions with DNA. Compounds <b>3c</b> and <b>4d</b> displayed a high probability of crossing the blood-brain barrier. The results support the potential of <b>3c</b> for future development as a dual-acting therapeutic agent in the prevention and/or treatment of Alzheimer's disease."],"journal":["Future medicinal chemistry"],"pubmed_title":["Design and synthesis of novel tacrine-indole hybrids as potential multitarget-directed ligands for the treatment of Alzheimer's disease."],"pmcid":["PMC8488533"],"funding_grant_id":["P50 AG025688","Grant 1/0016/18","NU20-08-00296","ERDF no.CZ.02.1.01/0.0/0.0/18069/0010054"],"pubmed_authors":["Bzonek P","Korabecny J","Mezencev R","Janockova J","Hrabinova M","Kuca K","Soukup O","Jun D","Ihnatova V","Hepnarova V","Novakova N","Hamulakova S","Janovec L","Deckner ZJ","Chernoff YO","Kudlickova Z"],"additional_accession":[]},"is_claimable":false,"name":"Design and synthesis of novel tacrine-indole hybrids as potential multitarget-directed ligands for the treatment of Alzheimer's disease.","description":"The authors report on the synthesis and biological evaluation of new compounds whose structure combines tacrine and indole moieties. Tacrine-indole heterodimers were designed to inhibit cholinesterases and β-amyloid formation, and to cross the blood-brain barrier. The most potent new acetylcholinesterase inhibitors were compounds <b>3c</b> and <b>4d</b> (IC<sub>50</sub> = 25 and 39 nM, respectively). Compound <b>3c</b> displayed considerably higher selectivity for acetylcholinesterase relative to human plasma butyrylcholinesterase in comparison to compound <b>4d</b> (selectivity index: IC<sub>50</sub> [butyrylcholinesterase]/IC<sub>50</sub> [acetylcholinesterase] = 3 and 0.6, respectively). Furthermore, compound <b>3c</b> inhibited β-amyloid-dependent amyloid nucleation in the yeast-based prion nucleation assay and displayed no dsDNA destabilizing interactions with DNA. Compounds <b>3c</b> and <b>4d</b> displayed a high probability of crossing the blood-brain barrier. The results support the potential of <b>3c</b> for future development as a dual-acting therapeutic agent in the prevention and/or treatment of Alzheimer's disease.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 May","modification":"2026-05-31T18:47:15.123Z","creation":"2025-04-05T22:17:35.27Z"},"accession":"S-EPMC8488533","cross_references":{"pubmed":["33829876"],"doi":["10.4155/fmc-2020-0184"]}}