Tacrine-sugar mimetic conjugates as enhanced cholinesterase inhibitors
Oliveira de Santana QL, Santos Evangelista TC, Imhof P, Ferreira SB, Fernández-Bolaños JG, Sydnes MO, Lopéz Ó, Lindbäck E (2021)
Publication Type: Journal article
Publication year: 2021
Journal
Book Volume: 19
Pages Range: 2322-2337
Journal Issue: 10
DOI: 10.1039/d0ob02588g
Abstract
We have used the Cu(i)-catalyzed azide-alkyne Huisgen cycloaddition reaction to obtain two families of bivalent heterodimers where tacrine is connected to an azasugar or iminosugar, respectively,vialinkers of variable length. The heterodimers were investigated as cholinesterase inhibitors and it was found that their activity increased with the length of the linker. Two of the heterodimers were significantly stronger acetylcholinesterase inhibitors than the monomeric tacrine. Molecular modelling indicated that the longer heterodimers fitted better into the active gorge of acetylcholinesterase than the shorter counterparts and the former provided more efficient simultaneous interaction with the tryptophan residues in the catalytic anionic binding site (CAS) and the peripheral anionic binding site (PAS).
Authors with CRIS profile
Involved external institutions
University of Stavanger / Universitetet i Stavanger
Norway (NO)
Universidade Federal do Rio de Janeiro (UFRJ) / Federal University of Rio de Janeiro
Brazil (BR)
University of Seville / Universidad de Sevilla
Spain (ES)
Norway (NO)
Universidade Federal do Rio de Janeiro (UFRJ) / Federal University of Rio de Janeiro
Brazil (BR)
University of Seville / Universidad de Sevilla
Spain (ES)
How to cite
APA:
Oliveira de Santana, Q.L., Santos Evangelista, T.C., Imhof, P., Ferreira, S.B., Fernández-Bolaños, J.G., Sydnes, M.O.,... Lindbäck, E. (2021). Tacrine-sugar mimetic conjugates as enhanced cholinesterase inhibitors. Organic & Biomolecular Chemistry, 19(10), 2322-2337. https://dx.doi.org/10.1039/d0ob02588g
MLA:
Oliveira de Santana, Quelli Larissa, et al. "Tacrine-sugar mimetic conjugates as enhanced cholinesterase inhibitors." Organic & Biomolecular Chemistry 19.10 (2021): 2322-2337.
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