| Title : Evaluation of N-alkyl isatins and indoles as acetylcholinesterase and butyrylcholinesterase inhibitors - Alcorn_2024_J.Enzyme.Inhib.Med.Chem_39_2286935 |
| Author(s) : Alcorn KN , Oberhauser IA , Politeski MD , Eckroat TJ |
| Ref : J Enzyme Inhib Med Chem , 39 :2286935 , 2024 |
| Abstract : Two series of N-alkyl isatins and N-alkyl indoles varying in size of the alkyl group were synthesised and evaluated for inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among the N-alkyl isatins 4a-j, the addition of the N-alkyl group improved inhibition potency towards AChE and BChE compared to isatin. Selectivity towards inhibition of BChE was observed, and the increase in size of the N-alkyl group positively correlated to improved inhibition potency. The most potent inhibitor for BChE was 4i (IC(50) = 3.77 microM, 22-fold selectivity for BChE over AChE). N-alkyl indoles 5a-j showed similar inhibition of AChE, the most potent being 5g (IC(50) = 35.0 microM), but 5a-j lost activity towards BChE. This suggests an important role of the 3-oxo group on isatin for BChE inhibition, and molecular docking of 4i with human BChE indicates a key hydrogen bond between this group and Ser198 and His438 of the BChE catalytic triad. |
| ESTHER : Alcorn_2024_J.Enzyme.Inhib.Med.Chem_39_2286935 |
| PubMedSearch : Alcorn_2024_J.Enzyme.Inhib.Med.Chem_39_2286935 |
| PubMedID: 38059272 |
Alcorn KN, Oberhauser IA, Politeski MD, Eckroat TJ (2024)
Evaluation of N-alkyl isatins and indoles as acetylcholinesterase and butyrylcholinesterase inhibitors
J Enzyme Inhib Med Chem
39 :2286935
Alcorn KN, Oberhauser IA, Politeski MD, Eckroat TJ (2024)
J Enzyme Inhib Med Chem
39 :2286935