A new series of pyridine derivatives with carbamic or amidic function has been designed and synthesized to act as cholinesterase inhibitors. The synthesized compounds were tested toward EeAChE and hAChE and toward eqBChE and hBChE. The carbamate 8 was the most potent hAChE inhibitor (IC50= 0.153 ± 0.016 μM) while the carbamate 11 was the most potent inhibitor of hBChE (IC50= 0.828 ± 0.067 μM). A molecular docking study indicated that the carbamate 8 was able to bind AChE by interacting with both CAS and PAS, in agreement with the mixed inhibition mechanism. Furthermore, the carbamates 8, 9 and 11 were able to inhibit Aβ42self-aggregation and possessed quite low toxicity against human astrocytoma T67 and HeLa cell lines, being the carbamate 8 the less toxic compound on both cell lines.

Pandolfi, F., De Vita, D., Bortolami, M., Coluccia, A., Di Santo, R., Costi, R., et al. (2017). New pyridine derivatives as inhibitors of acetylcholinesterase and amyloid aggregation. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 141, 197-210 [10.1016/j.ejmech.2017.09.022].

New pyridine derivatives as inhibitors of acetylcholinesterase and amyloid aggregation

Andrisano, Vincenza;Bergamini, Christian;Fato, Romana;Bartolini, Manuela;
2017

Abstract

A new series of pyridine derivatives with carbamic or amidic function has been designed and synthesized to act as cholinesterase inhibitors. The synthesized compounds were tested toward EeAChE and hAChE and toward eqBChE and hBChE. The carbamate 8 was the most potent hAChE inhibitor (IC50= 0.153 ± 0.016 μM) while the carbamate 11 was the most potent inhibitor of hBChE (IC50= 0.828 ± 0.067 μM). A molecular docking study indicated that the carbamate 8 was able to bind AChE by interacting with both CAS and PAS, in agreement with the mixed inhibition mechanism. Furthermore, the carbamates 8, 9 and 11 were able to inhibit Aβ42self-aggregation and possessed quite low toxicity against human astrocytoma T67 and HeLa cell lines, being the carbamate 8 the less toxic compound on both cell lines.
2017
Pandolfi, F., De Vita, D., Bortolami, M., Coluccia, A., Di Santo, R., Costi, R., et al. (2017). New pyridine derivatives as inhibitors of acetylcholinesterase and amyloid aggregation. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 141, 197-210 [10.1016/j.ejmech.2017.09.022].
Pandolfi, Fabiana; De Vita, Daniela; Bortolami, Martina; Coluccia, Antonio; Di Santo, Roberto; Costi, Roberta; Andrisano, Vincenza; Alabiso, Francesco...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/612826
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