1. Synthesis, Crystal Structure, and Biological Evaluation of Fused Thiazolo[3,2- a ]Pyrimidines as New Acetylcholinesterase Inhibitors.
- Author
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Mahgoub MY, Elmaghraby AM, Harb AA, Ferreira da Silva JL, Justino GC, and Marques MM
- Subjects
- Acetylcholinesterase drug effects, Cholinesterase Inhibitors chemistry, Crystallography, X-Ray, Humans, Molecular Docking Simulation, Pyrimidines chemistry, Tandem Mass Spectrometry, Acetylcholinesterase chemistry, Cholinesterase Inhibitors chemical synthesis, Pyrimidines chemical synthesis
- Abstract
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 5 H cyclization of the dihydropyrimidinethiones. All target compounds were evaluated in vitro as human acetylcholinesterase ( h AChE) inhibitors via an Ellman-based colorimetric assay and showed good inhibition activities (better than 70% at 10 µM and IC
50 values in the 1 µM range). Molecular docking simulations for all target products into h AChE 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.- Published
- 2019
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