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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholinesterase / chemistry
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Alzheimer Disease / drug therapy*
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Animals
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Butyrylcholinesterase / chemistry
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Cholinesterase Inhibitors / chemical synthesis*
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Cholinesterase Inhibitors / pharmacology
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Cholinesterase Inhibitors / toxicity
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In Vitro Techniques
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Liver / drug effects*
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Liver / metabolism
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Muscle Relaxation
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Nitric Oxide Donors / chemical synthesis*
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Nitric Oxide Donors / pharmacology
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Nitric Oxide Donors / toxicity
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Pulmonary Artery / drug effects
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Pulmonary Artery / physiology
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Structure-Activity Relationship
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Swine
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Tacrine / analogs & derivatives*
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Tacrine / chemical synthesis*
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Tacrine / pharmacology
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Tacrine / toxicity
Substances
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Cholinesterase Inhibitors
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Nitric Oxide Donors
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Tacrine
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Acetylcholinesterase
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Butyrylcholinesterase