Synthesis, Crystal Structure, and Biological Evaluation of Fused Thiazolo[3,2-a]Pyrimidines as New Acetylcholinesterase Inhibitors.
Mohamed Y MahgoubAwatef M ElmaghrabyAbd-Elfttah A HarbJoão Luís Ferreira da SilvaGonçalo C JustinoMaria Matilde MarquesPublished in: Molecules (Basel, Switzerland) (2019)
A new series of thiazolo[3,2-a]pyrimidine bromide salt derivatives 7a-d were synthesized from 3,4-dihydropyrimidinethione precursors. The target compounds were fully characterized by 1D- and 2D-NMR, high resolution ESI-MS/MS and single crystal X-ray diffraction analysis, which confirmed a regioselective 5H cyclization of the dihydropyrimidinethiones. All target compounds were evaluated in vitro as human acetylcholinesterase (hAChE) inhibitors via an Ellman-based colorimetric assay and showed good inhibition activities (better than 70% at 10 µM and IC50 values in the 1 µM range). Molecular docking simulations for all target products into hAChE were performed and confirmed strong binding to the enzyme. These results provide a promising and new starting point to improve acetylcholinesterase inhibitors and explore novel treatment options against Alzheimer's disease.
Keyphrases
- high resolution
- crystal structure
- molecular docking
- ms ms
- endothelial cells
- molecular dynamics simulations
- gold nanoparticles
- magnetic resonance
- high throughput
- hydrogen peroxide
- molecular dynamics
- solid state
- computed tomography
- single cell
- tandem mass spectrometry
- electron microscopy
- single molecule
- data analysis
- ultra high performance liquid chromatography