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Title: Design, Synthesis and Bioassays of 3-substituted-3-hydroxyoxindoles for cholinesterase inhibition
Authors: Totobenazara, Jane
Caldeira, Teresa
Martins, Rosário
Burke, Anthony
Editors: Astruc, Didier
Keywords: Medicinal
Issue Date: 1-Aug-2016
Publisher: ChemPubSoc Europe
Abstract: Based on the positive bioassay results of the known oxindole hit compound rac-1-benzyl-3-hydroxy-3-phenylindolin-2-one which showed significant inhibition of butyrylcholinesterase (BuChE) (IC50=7.41 μM), a library of 31 analogues of 3-substituted-3-hydroxyoxindoles was synthesized and screened for both acetylcholinesterase (AChE) and BuChE activity. Our bioassays revealed that some of the new compounds exhibited moderate inhibition of eel AChE (EeAChE) and very good inhibition of equine serum BuChE (EqBuChE) with a best IC50 of 1.02 μM. On the basis of these results, the lead compound 1-((1-benzylpiperidin-4-yl)methyl)-3-hydroxy-3-phenylindolin-2-one was designed, which was shown to interact well with the enzymes active sites by molecular docking, was synthesized and upon bioassay gave an IC50 of 6.61 μM for BuChE. Interestingly, when we separated rac-benzyl-3-hydroxy-3-phenylindolin-2-one into the individual enantiomers (R)- and (S)-benzyl-3-hydroxy-3-phenylindolin-2-one it was the latter enantiomer that gave the best IC50 of 6.19 μM for BuChE.
Type: article
Appears in Collections:CQE - Publicações - Artigos em Revistas Internacionais Com Arbitragem Científica

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