Synthesis and biological evaluation of NO-donor-tacrine hybrids as hepatoprotective anti-Alzheimer drug candidates.

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Fang L, Appenroth D, Decker M, Kiehntopf M, Roegler C, Deufel T, Fleck C, Peng S, Zhang Y, Lehmann J

Synthesis and biological evaluation of NO-donor-tacrine hybrids as hepatoprotective anti-Alzheimer drug candidates.

J Med Chem. 2008 Feb 28;51(4):713-6. doi: 10.1021/jm701491k. Epub 2008 Jan 31.

PubMed ID
18232655 [ View in PubMed
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Abstract

In search of safer anti-Alzheimer drugs, 14 NO-donor-tacrine hybrids (1- 14) were synthesized and evaluated for their ability to inhibit cholinesterases and for vasorelaxation effects. Compounds 1- 13 showed good cholinesterases inhibitory activities in vitro, while 14, particularly, was highly selective, preferring butyrylcholinesterase rather than acetylcholinesterase. Four selected compounds (1, 9, 11, and 14) moderately relaxed the porcine pulmonary arteries in organ bath. In the hepatotoxicity study, significant hepatotoxicity was caused by tacrine but not by 9.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
TacrineAcetylcholinesteraseIC 50 (nM)45.1N/AN/ADetails