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1-N-Substituted thiocarbamoyl-3-phenyl-5-thienyl-2-pyrazolines: a novel cholinesterase and selective monoamine oxidase B inhibitors for the treatment of Parkinson's and Alzheimer's diseases.

Twelve 1-N-substituted thiocarbamoyl-3-phenyl-5-thienyl-2-pyrazoline derivatives were synthesized and their biological interactions with human plasma and erythrocyte acetylcholinesterase (AChE) and butrylcholinesterase (BuChE) enzymes were assessed. Compounds 3i-3l of newly synthesized N-substituted pyrazolines, which were presented as selective and irreversible MAO-B inhibitors in our previous report, were found to inhibit human erythrocyte and plasma AChE activities selectively and non-competitively suggesting that these compounds may interact with a region close to the peripheral site of the enzyme molecule which could shift the proper positioning of the catalytic center. Compounds 3e-3h inhibited both AChE and BuChE activities of human erythrocytes, but the inhibitory potencies of these compounds towards BuChE were found to be higher than that of towards AChE. Inhibition was found to be non-competitive and reversible. These data suggested that newly synthesized N-substituted pyrazoline derivatives can be evaluated as both MAO-B and cholinesterase inhibitors which may have promising features in the treatment of Alzheimer's and Parkinson's diseases.

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