Tacrine-sugar mimetic conjugates as enhanced cholinesterase inhibitors.
Org Biomol Chem
; 19(10): 2322-2337, 2021 03 18.
Article
in En
| MEDLINE
| ID: mdl-33645607
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, via linkers 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).
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tacrine
/
Cholinesterase Inhibitors
/
Imino Sugars
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Org Biomol Chem
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2021
Document type:
Article