25-08-2017, 09:32 PM
19-09-2017, 03:20 PM
Based on the pharmacological importance of dihydropyrimidine scaffolding (DHPM), substituted DHPMs attached to an acetamide linker were substituted for substituted aromatic anilines and their potency as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors were synthesized. The good AChE inhibitory activity of the 4-dihydropyrimidine-2-thione (4a-h) and 2-amino-1,4-dihydropyrimidine (5a-h) series was observed with the compounds 4a and 4d identified as the compounds more potent with IC 50 values of 0.17 ± 0.01 and 0.39 ± 0.04 μM respectively. Inhibition of BChE was found over a broader range of concentrations (2.37-56.32 μM). To explore the binding observations in the enzyme, the molecular coupling study was carried out using the GOLD software. Binding mode analysis indicated that all of these inhibitors are well accommodated at the active site and interact with the key amino acid residues of the catalytic anionic site (CAS) and the peripheral anion site (PAS). In addition, in silico ADMET predictions suggest that these compounds are non-AMES toxic with good blood-brain barrier (BBB) penetration, human intestinal absorption.