English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

In a continuation of our previous work for the exploration of novel enzyme inhibitors, two new coumarin-thiazole  6(a–o)  and coumarin-oxadiazole  11(a–h)  hybrids have been designed and synthesized. All the compounds were characterized by  1 H- and  13 C-NMR spectroscopy and elemental analysis. New hybrid analogs were evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in order to know their potential for the prevention of Alzheimer's disease (AD). In coumarinyl thiazole series, compound  6b  was found as the most active member against AChE having IC 50  value of 0.87 ± 0.09 μM, while the compound  6j  revealed the same efficacy against BuChE with an IC 50  value of 11.01 ± 3.37 μM. In case of coumarinyl oxadiazole series,  11a  was turned out to be the lead candidate against AChE with an IC 50  value of 6.07 ± 0.23 μM, whereas compound  11e  was found significantly active against BuChE with an IC 50  value of 0.15 ± 0.09 μM. To realize the binding interaction of these compounds with AChE and BuChE, the molecular docking studies were performed. Compounds from coumarinyl thiazole series with potent AChE activity ( 6b ,  6h ,  6i , and  6k ) were found to interact with AChE in the active site with MOE score of −10.19, −9.97, −9.68, and −11.03 Kcal.mol −1 , respectively. The major interactions include hydrogen bonding, π-π stacking with aromatic residues, and interaction through water bridging. The docking studies of coumarinyl oxadiazole derivatives  11(a–h)  suggested that the compounds with high anti-butyrylcholinesterase activity ( 11e ,  11a , and  11b ) provided MOE score of −9.9, −7.4, and −8.2 Kcal.mol −1 , respectively, with the active site of BuChE building π-π stacking with Trp82 and water bridged interaction.

Combined in Vitro and in Silico Studies for the Anticholinesterase Activity and Pharmacokinetics of Coumarinyl Thiazoles and Oxadiazoles