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Dostęp zamknięty“Clicking“ fragment leads to novel dual-binding cholinesterase inhibitors
| cris.lastimport.scopus | 2024-02-12T20:12:23Z |
| dc.abstract.en | Cholinesterase inhibitors are potent therapeutics in the treatment of Alzheimer's disease. Among them, dual binding ligands have recently gained a lot of attention. We discovered novel dual-binding cholinesterase inhibitors, using “clickable” fragments, which bind to either catalytic active site (CAS) or peripheral anionic site (PAS) of the enzyme. Copper(I)-catalyzed azide-alkyne cycloaddition allowed to effectively synthesize a series of final heterodimers, and modeling and kinetic studies confirmed their ability to bind to both CAS and PAS. A potent acetylcholinesterase inhibitor with IC50 = 18 nM (compound 23g) was discovered. A target-guided approach to link fragments by the enzyme itself was tested using butyrylcholinesterase. |
| dc.affiliation | Uniwersytet Warszawski |
| dc.contributor.author | Monjas, Leticia |
| dc.contributor.author | Molęda, Zuzanna |
| dc.contributor.author | Czarnocki, Zbigniew |
| dc.contributor.author | Zawadzka, Anna |
| dc.contributor.author | Hirsch, Anna K.H. |
| dc.contributor.author | Budzianowski, Armand |
| dc.contributor.author | Maurin, Jan |
| dc.date.accessioned | 2024-01-24T19:25:10Z |
| dc.date.available | 2024-01-24T19:25:10Z |
| dc.date.issued | 2021 |
| dc.description.finance | Publikacja bezkosztowa |
| dc.description.volume | 42 |
| dc.identifier.doi | 10.1016/J.BMC.2021.116269 |
| dc.identifier.issn | 0968-0896 |
| dc.identifier.uri | https://repozytorium.uw.edu.pl//handle/item/103130 |
| dc.identifier.weblink | https://doi.org/10.1016/j.bmc.2021.116269 |
| dc.language | eng |
| dc.pbn.affiliation | chemical sciences |
| dc.relation.ispartof | Bioorganic and Medicinal Chemistry |
| dc.relation.pages | art. no. 116269 |
| dc.rights | ClosedAccess |
| dc.sciencecloud | nosend |
| dc.subject.en | Combinatorial libraries |
| dc.subject.en | Galantamine |
| dc.subject.en | Hybrid drugs |
| dc.subject.en | Structure-activity relationship |
| dc.subject.en | Target-guided synthesis |
| dc.subject.en | Tetrahydroisoquinoline |
| dc.subject.en | Triazole |
| dc.subject.en | Tryptamine |
| dc.subject.en | ”click” chemistry |
| dc.title | “Clicking“ fragment leads to novel dual-binding cholinesterase inhibitors |
| dc.type | JournalArticle |
| dspace.entity.type | Publication |