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Tacrine-ferulic acid-nitric oxide (NO) donor trihybrids as potent, multifunctional acetyl- and butyrylcholinesterase inhibitors.
- Source :
-
Journal of medicinal chemistry [J Med Chem] 2012 May 10; Vol. 55 (9), pp. 4309-21. Date of Electronic Publication: 2012 Apr 27. - Publication Year :
- 2012
-
Abstract
- In search of multifunctional cholinesterase inhibitors as potential anti-Alzheimer drug candidates, tacrine-ferulic acid-NO donor trihybrids were synthesized and tested for their cholinesterase inhibitory activities, release of nitric oxide, vasodilator properties, cognition improving potency, and hepatotoxicity. All of the novel target compounds show higher in vitro cholinesterase inhibitory activity than tacrine. Three selected compounds (3a, 3f, and 3k) produce moderate vasorelaxation in vitro, which correlates with the release of nitric oxide. Compared to its non-nitrate dihybrid analogue (3u), the trihybrid 3f exhibits better performance in improving the scopolamine-induced cognition impairment (mice) and, furthermore, less hepatotoxicity than tacrine.
- Subjects :
- Alzheimer Disease drug therapy
Animals
Behavior, Animal drug effects
Binding Sites physiology
Biphenyl Compounds chemistry
Cholinesterase Inhibitors chemistry
Cholinesterase Inhibitors pharmacology
Coumaric Acids chemical synthesis
Coumaric Acids chemistry
Humans
Inhibitory Concentration 50
Kinetics
Liver metabolism
Liver pathology
Magnetic Resonance Spectroscopy
Male
Mice
Mice, Inbred ICR
Models, Molecular
Nitric Oxide metabolism
Nitric Oxide Donors chemistry
Nitric Oxide Donors pharmacology
Picrates chemistry
Spectrometry, Mass, Electrospray Ionization
Structure-Activity Relationship
Tacrine chemistry
Tacrine pharmacology
Vasodilation drug effects
Butyrylcholinesterase metabolism
Cholinesterase Inhibitors chemical synthesis
Coumaric Acids pharmacology
Nitric Oxide Donors chemical synthesis
Tacrine analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1520-4804
- Volume :
- 55
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 22512543
- Full Text :
- https://doi.org/10.1021/jm300106z