Date of Award

Fall 1980

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry & Biochemistry

Program/Concentration

Chemistry

Committee Director

Roy L. Williams

Committee Member

Billy T. Upchurch

Committee Member

James H. Yuan

Call Number for Print

Special Collections LD4331.C45 L86

Abstract

Objectives of this research were to (1) synthesize, and (2) evaluate new compounds which would be potential reactivators of organophosphate-inhibited acetylcholinesterase.

A series of 1,8-diazafluorenone and 2,2'bipyridylketone oximes and oxime methiodides were synthesized (11, 13, 14, 22, 24). These compounds were developed as structural analogs of 2-PAM (2-Pyridinealdoxime methiodide) and TMB-4 (1,1Trimethylene-Bis(4-formylpyridinium bromide)dioxime), the current drugs of choice for treatment of organophosphorous poisoning.

Acetylcholinesterase from electric eel was inhibited with DFP (diisopropylfluorophosphate), an irreversible-type inhibitor, and the inhibited enzyme was treated with the various reactivator compounds. The reactivation assays were monitored with pH stat apparatus, and the data were evaluated according to the method of Kitz and Ginsburg (36). Relative reactivation rates, as compared to 2-PAM, the standard and reference drug, were calculated for each of the targeted compounds.

One of the compounds tested, bipyridylketone oxime methiodide, 24, was found to have substantial reactivation ability. A second compound, diazafluorenone oxime methiodide, 14, had a reactivation rate which was considerably less than that of 24, but which was still greater than that of the reference drug, 2-PAM.

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DOI

10.25777/sgxq-gb14

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