Biological evaluation, molecular docking, and SAR studies of novel 2-(2,4-dihydroxyphenyl)-1H- benzimidazole analogues

Abstrakt

In the present study, new 4-(1H-benzimidazol-2-yl)-benzene-1,3-diols, modified in both rings, have been synthesized and their efficacies as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors have been determined. The modified Ellman’s spectrophotometricmethodwasappliedforthebiologicalevaluation. Thecompoundsshowedstrong (IC50 80–90 nM) AChE and moderate (IC50 5–0.2 µM) BuChE inhibition in vitro. Some compounds were effective toward AChE/BuChE, exhibiting high selectivity ratios versus BuChE, while the other compounds were active against both enzymes. The structure–activity relationships were discussed. The compounds inhibited also in vitro self-induced Aβ(1–42) aggregation and exhibited antioxidant properties. The docking simulations showed that the benzimidazoles under consideration interact mainly with the catalytic site of AChE and mimic the binding mode of tacrine.

Autorzy

Monika Karpińska
Monika Karpińska
Kamila Czarnecka
Kamila Czarnecka
Agata Szymańska
Agata Szymańska
Paweł Szymański
Paweł Szymański
Marek Bajda
Marek Bajda
artykuł
Biomolecules
Angielski
2019
9
12
870
otwarte czasopismo
CC BY 4.0 Uznanie autorstwa 4.0
ostateczna wersja opublikowana
w momencie opublikowania
2019-12-12
100
4,082
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