Synthesis of aromatics oximes and hydrazones with electrowithdrawing substituents as reactivators of Acetylcholinesterase

Synthesis of aromatics oximes and hydrazones with electrowithdrawing substituents as reactivators of Acetylcholinesterase

Petronilho, E. C.; Pinto, A. C.; Figueroa-Villar, J. D.

Abstract:

Neurotoxic organophosphates inhibit acetylcholinesterase (AChE) through a fosfilation process of serine involved in the hydrolysis of the neurotransmitter acetylcholine (ACh), which causes a cholinergic syndrome and eventual death from respiratory failure. There are several ways of treating intoxication by organophosphorus compounds (OPs), the AChE reactivators are oximes cationic as the pralidoxime (2-PAM) (3), but none of them is efficient against all the known neurotoxic agents or against all of their effects, thus demonstrating the need for development of compounds as drug candidates, being potent, selective and with a low toxicity profile to allow the treatment of poisoning caused by chemical warfare agents and pesticides. A study using molecular modeling with ab initio methods suggested the evaluation of nucleophiles different from oximes, such as hydrazones.

Neurotoxic organophosphates inhibit acetylcholinesterase (AChE) through a fosfilation process of serine involved in the hydrolysis of the neurotransmitter acetylcholine (ACh), which causes a cholinergic syndrome and eventual death from respiratory failure. There are several ways of treating intoxication by organophosphorus compounds (OPs), the AChE reactivators are oximes cationic as the pralidoxime (2-PAM) (3), but none of them is efficient against all the known neurotoxic agents or against all of their effects, thus demonstrating the need for development of compounds as drug candidates, being potent, selective and with a low toxicity profile to allow the treatment of poisoning caused by chemical warfare agents and pesticides. A study using molecular modeling with ab initio methods suggested the evaluation of nucleophiles different from oximes, such as hydrazones.

Palavras-chave:

DOI: 10.5151/chempro-15bmos-BMOS2013_2013915225733

Referências bibliográficas

• [1] 1Delfino, R. T., Ribeiro, T. S. And Figueroa-Villar J. D. J. Braz.
• [2] Chem. Soc., 2009, 20: 407–428.
• [3] 2 Delfino, R. T. And Figueroa-Villar, J. D. J. Phys.Chem.B. 2009,
• [4] 113: 8402-8411.

Como citar:

Petronilho, E. C.; Pinto, A. C.; Figueroa-Villar, J. D.; "Synthesis of aromatics oximes and hydrazones with electrowithdrawing substituents as reactivators of Acetylcholinesterase", p-279-279. In: In Blucher Chemistry Proceedings, São Paulo, v. 1, n. 2, Dezembro.2013. São Paulo: Blucher, 2013.
ISSN 23184043, DOI 10.5151/chempro-15bmos-BMOS2013_2013915225733