Dissertation/Thesis Abstract

Aryl dibutyl phosphates, racemic and enantiomerically enriched alkyl aryl cholinyl phosphates, and tetraalkyl bisphosphates: Their synthesis and study as organophosphorus inhibitors of butyrylcholinesterase
by Tran, Trina, M.S., California State University, Long Beach, 2016, 153; 10161777
Abstract (Summary)

Alzheimer’s disease (AD) is the most common cause of dementia among older people characterized by low concentration of acetylcholine in the brain. Butyrylcholinesterase (BChE) is one of the two cholinesterase enzymes that catalyze the hydrolysis of acetylcholine into choline and acetic acid, and its activity is found to be increased above normal in AD patients. Therefore, BChE inhibitors may help to increase acetylcholine concentration in the brain and hold promise in the treatment of the disease. To search for the most effective BChE inhibitors, we were interested in the synthesis of structurally different organophosphates and their interaction with BChE.

A variety of organophosphates divided into three main types of scaffolds were synthesized and evaluated in vitro for their activity against BChE. Di-n-butyl aryl phosphates (DBAPs) were found to be selective inhibitors of BChE, especially when placing methyl groups on the phenyl ring. Racemic and optically active alkyl aryl cholinyl phosphates (AACPs) were successfully synthesized by using the methods we developed in our laboratory, and these analogs were stronger BChE inhibitors than DBAPs, particularly when the alkyl chain was lengthened. Also, a library of tetraalkyl bisphosphates with both oxygen and sulfur containing linkers were synthesized and their inhibitory abilities examined. At this time, we observed that the six carbon chain is the optimal linker chain length and the sulfur atom containing linker exhibited higher inhibition than the oxygen atom containing linker.

Indexing (document details)
Advisor: Nakayama, Kensaku
Commitee: Buonora, Paul T., Marinez, Eric R.
School: California State University, Long Beach
Department: Chemistry and Biochemistry
School Location: United States -- California
Source: MAI 56/01M(E), Masters Abstracts International
Subjects: Chemistry, Biochemistry
Publication Number: 10161777
ISBN: 978-1-369-16639-2
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