1. Design, Synthesis, and Biological Evaluation of a New Series of Biphenyl/Bibenzyl Derivatives Functioning as Dual Inhibitors of Acetylcholinesterase and Butyrylcholinesterase
- Author
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Bo Feng, Lin Wang, Song Wu, Hui Fu, Guanhua Du, Wang Dongmei, and Ai-Lin Liu
- Subjects
0301 basic medicine ,biphenyl/bibenzyl derivatives ,Aché ,Stereochemistry ,Pharmaceutical Science ,Pharmacology ,Article ,Analytical Chemistry ,lcsh:QD241-441 ,03 medical and health sciences ,chemistry.chemical_compound ,Structure-Activity Relationship ,0302 clinical medicine ,lcsh:Organic chemistry ,Alzheimer Disease ,Drug Discovery ,Bibenzyls ,Bibenzyl ,Animals ,Humans ,Physical and Theoretical Chemistry ,IC50 ,Butyrylcholinesterase ,Biological evaluation ,Biphenyl ,Organic Chemistry ,Biphenyl Compounds ,molecular docking ,Acetylcholinesterase ,language.human_language ,Alzheimer’s disease ,acetylcholinesterase inhibitors ,butyrylcholinesterase inhibitors ,Rats ,Molecular Docking Simulation ,030104 developmental biology ,chemistry ,Design synthesis ,Chemistry (miscellaneous) ,Drug Design ,language ,Molecular Medicine ,Cholinesterase Inhibitors ,030217 neurology & neurosurgery - Abstract
Alzheimer's disease (AD), the most common form of dementia in adults, is a progressive neurodegenerative disorder of the brain characterized by loss of memory and steady deterioration of cognition. Here, a series of symmetrical molecules containing biphenyl/bibenzyl scaffolds (12-36) were designed, synthesized, and evaluated for their ability to inhibit both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). A biological evaluation showed that most of these biphenyl derivatives were potent AChE and BuChE inhibitors. Among them, compound 15 displayed the greatest ability to inhibit BuChE (IC50 = 0.74 µM) and was also a good AChE inhibitor (IC50 = 1.18 µM). Compound 19 was not only a potent AChE inhibitor (IC50 = 0.096 µM), but also a mild BuChE inhibitor (IC50 =1.25 µM). Overall, these results suggested that compound 19 may be a promising agent in the treatment of AD.
- Published
- 2017