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Study of new acetylcholinesterase modulators
 Račáková, Veronika ; Opletalová, Veronika (advisor) ; Pohanka, Miroslav (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control Candidate: Mgr. Veronika Račáková Consultant: Assoc. Prof. RNDr. Veronika Opletalová, Ph.D. Title of Thesis: Study of new acetylcholinesterase modulators. Organophosphorus compounds are chemically organophosphates or organophosphonates. They have been widely used as a pesticides but because of their high toxicity and relatively cheap and easy synthesis they can be easily misused as chemical weapons - nerve paralytic compounds. Toxic effect of these compounds is based on irreversible inhibition of the enzyme acetylcholinesterase (AChE). In case of intoxication by these compounds anticholinergic drugs (atropin) and reactivators of AChE are usually used as antidots. The effect of the reactivators is based on splitting the complex enzyme-inhibitor. Pralidoxim, trimedoxim, obidoxim and asoxim (HI-6) are still the most often used reactivators all over the world. They are the compounds which contain oxime group and one or two quarternary nitrogens in their molecule, what ensures that their affinity to AChE will be strong enough. Screening and synthesis of new more effective broad-spectrum reactivators of AChE with lower side effects is still very actual and discussed theme. Strategy...
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