Synthesis of novel carboxamide- and carbohydrazide-benzimidazoles as selective butyrylcholinesterase inhibitors
MOLECULAR DIVERSITY, cilt.26, sa.5, ss.2863-2876, 2022 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 26 Sayı: 5
- Basım Tarihi: 2022
- Doi Numarası: 10.1007/s11030-022-10476-8
- Dergi Adı: MOLECULAR DIVERSITY
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE
- Sayfa Sayıları: ss.2863-2876
- Anahtar Kelimeler: Alzheimer's disease, Benzimidazole, Cholinesterase inhibitors, Cytotoxicity, Molecular docking, HISTIDINE PROTONATION, PREDICTION, SOLUBILITY, TARGET
- Ankara Üniversitesi Adresli: Evet
Özet
Selectively inhibiting butyrylcholinesterase (BChE) is hypothesized to help in the management of Alzheimer's disease (AD). Several studies have determined a correlation between the increased activity of BChE and the onset of AD. An advantage of BChE over acetylcholinesterase inhibition is that absence of BChE activity does not lead to obvious physiological disturbance. However, currently no BChE inhibitors are available commercially as potential therapeutics for AD. In our continuous effort to find potent BChE inhibitors for Alzheimer's disease, a total of 22 novel benzimidazoles with diversified substitutions were synthesized and evaluated for their anticholinesterase activities in this study. Among the synthesized compounds, 2j and 3f were found to exhibit potent and selective BChE inhibition with IC50 values of 1.13 and 1.46 mu M, respectively. Molecular docking studies were carried out to rationalize the observed inhibitory activities. The compounds were predicted to have high penetration across the blood-brain barrier. Moreover, cell proliferative studies were also performed to evaluate the toxicity profile of the interested compounds.