Processos de biotransformação oxidativa de pesticidas organofosfotioatos e inibição da acetilcolinesterase: cálculos de interação e mecanismo de reação

• Ano de defesa: 2023
• Autor(a) principal: Militani, Isabela Aparecida
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Lavras; Programa de Pós-graduação em Agroquímica; UFLA; brasil; Departamento de Química
• Palavras-chave em Português: Química computacional; Pesticidas; Biotransformação oxidativa; Inibição da HssAChE; Acoplamento molecular; QM/MM; Computational chemistry; Pesticides; Oxidative biotransformation; HssAChE inhibition; Molecular docking; Quantum mechanics/Molecular mechanics (QM/MM); Fisico-Química
• Link de acesso: http://repositorio.ufla.br/jspui/handle/1/55950

Agrochemicals have lethal properties capable of controlling or eliminating a living organism, that is, they block the organisms' vital metabolic processes. They cause serious problems for human health, as they are highly toxic. The most used pesticides that are considered toxic are known as organophosphothioates (OP/P=S) in their commercialized form and organophosphates (OP/P=O) in their active form. These compounds have been the subject of studies on their metabolism and toxicology. According to research carried out, the toxicity of these pesticides is increased when oxidative metabolic desulfurization reactions occur, where the OP/P=S are transformed into OP/P=O. This toxicity is due to the ability of OP/P=O species to inhibit the human acetylcholinesterase enzyme (HssAChE). Based on this context, the objective of this work was to study the oxidative biotransformation of OP/P=S pesticides and the inhibition of the HssAChE enzyme by OP/P=S and OP/P=O using the molecular docking technique and QM/MM calculations. The theoretical results obtained showed that in the oxidative biotransformation process, parathion is the compound with the greatest ability to transform OF/P=S into OP/P=O, thus forming the active paraoxon metabolite. In the HssAChE enzyme inhibition by OP/P=S and OP/P=O, our results showed that of all the compounds investigated, those with the highest inhibitory activities are parathion, paraoxon, malathion, diazoxon, chlorpyrifos and omethoate. This study was essential due to the lack of information in the literature about the oxidative biotransformation process of OP/P=S pesticides, as well as the ability of these compounds to inhibit HssAChE enzyme. With this study, it was possible to observe that, in the oxidative biotransformation, chlorpyrifos and parathion have greater capacities to transform into their active metabolites and in the inhibition of the HssAChE enzyme, it was possible to observe that not all OP/P=O are the ones with the highest abilities to inhibit the HssAChE enzyme.