Synthesis and evaluation of novel arylisoxazoles linked to tacrine moiety: in vitro and in vivo biological activities against Alzheimer's disease.

Alzheimer's disease (AD) is now ranked as the third leading cause of death after heart disease and cancer. There is no definite cure for AD due to the multi-factorial nature of the disease, hence, multi-target-directed ligands (MTDLs) have attracted lots of attention. In this work, focusing on the efficient cholinesterase inhibitory activity of tacrine, design and synthesis of novel arylisoxazole-tacrine analogues was developed.

Novel N-benzylpyridinium moiety linked to arylisoxazole derivatives as selective butyrylcholinesterase inhibitors: Synthesis, biological evaluation, and docking study.

A novel series of N-benzylpyridinium moiety linked to arylisoxazole ring were designed, synthesized, and evaluated for their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. Synthesized compounds were classified into two series of 5a-i and 5j-q considering the position of positively charged nitrogen of pyridinium moiety (3- or 4- position, respectively) connected to isoxazole carboxamide group. Among the synthesized compounds, compound 5n from the second series of compounds possessing 2,4-dichloroaryl group connected to isoxazole ring was found to be the most potent AChE inhibitor (IC = 5.

Design and synthesis of novel coumarin-pyridinium hybrids: In vitro cholinesterase inhibitory activity.

A novel series of coumarin-pyridinium hybrids were synthesized and evaluated as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using Ellman's method. Among synthesized compounds, 1-(3-fluorobenzyl)-4-((2-oxo-2H-chromene-3-carboxamido)methyl)pyridinium bromide (7l) was found to be the most active compound toward AChE (IC = 10.14 µM), 1-(3-chlorobenzyl)-3-((2-oxo-2H-chromene-3-carboxamido)methyl)pyridinium bromide (7g) and 1-(2,3-dichlorobenzyl)-3-((2-oxo-2H-chromene-3-carboxamido)methyl)pyridinium chloride (7h) depicted the best BChE inhibitory activity (ICs = 0.

Novel tacrine-1,2,3-triazole hybrids: In vitro, in vivo biological evaluation and docking study of cholinesterase inhibitors.

A new series of tacrine-1,2,3-triazole hybrids were designed, synthesized, and evaluated as potent dual cholinesterase inhibitors. Most of synthesized compounds showed good in vitro inhibitory activities toward both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among them, 7-chloro-N-((1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl)-1,2,3,4-tetrahydroacridin-9-amine (5l) was found to be the most potent anti-AChE derivative (IC = 0.