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Development of indanones and isatins as non-cytotoxic inhibitors of cholinesterases

Josephine M. Gießel, Anne Loesche, Sophie Hoenke, Immo Serbian, Ahmed Al-Harrasi, Rene Csuk


A small library of indanone-amides and substituted isatin derivatives has been prepared; these compounds have been investigated for their ability to act as inhibitors for the enzymes acetyl- and butyrylcholinesterase (AChE, BChE). Several of them were moderate inhibitors for AChE and not cytotoxic for a variety of human tumor cell lines as well as for non-malignant mouse fibroblasts. In this library consisting of 49 derivatives, 5,7-dibromo-4-iodoisatin was shown to be a good mixed-type inhibitor for AChE (K­i = 2.52 ± 0.61 µM and K = 11.74 ± 1.31 µM) but this compound also acted as a dual inhibitor for BChE (Ki = 4.49 ± 0.32 µM and K = 6.56 ± 0.57 µM). Interestingly, N-hexyl-1-oxo-2,3-dihydro-1H-indene-2-carboxamide was cytotoxic especially for MCF-7 breast adenocarcinoma cells (EC50 = 4.28 ± 0.5 µM).

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