Planejamento por Docagem e Dinâmica Molecular de pesticidas inibidores da Acetilcolinesterase do mosquito Aedes aegypti

• Ano de defesa: 2021
• Autor(a) principal: Guerra, Isadóra Aurora
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal do Espírito Santo; BR; Mestrado em Química; Centro de Ciências Exatas; UFES; Programa de Pós-Graduação em Química
• Palavras-chave em Português: Acetilcolinesterase; dinâmica molecular; docagem molecular; pesticidas organofosforados; mosquito Aedes aegypti; subject.br-rjbn; Química
• Link de acesso: http://repositorio.ufes.br/handle/10/15650

The use of insecticides appears as one of the strategies to prevent arboviruses such as Zika, Chikungunya, dengue and malaria, since they help to control the proliferation of mosquitoes. However, organophosphate pesticides are high toxicity to mammals, and can cause poisoning and eventual death to users. In this work, we carried out studies by docking and molecular dynamics of the acetylcholinesterase enzymes from the mosquito Aedes aegypti (AaAChE) and from Homo sapiens sapiens (HssAChE) with nineteen pesticides, of which six were reported for use in Anophele gambiae mosquitoes, paraoxon as comparison and six new proposals that were planned from the addition of pharmacophoric groups interacting with mutant tyrosines at the entry of the active site of the enzyme AaAChE. Results show that the Gibbs free energy estimated by the MM-PBSA method of the complexes PM22-AaAChE, PROP2-AaAChE and PROP3-AaAChE showed greater stability when compared to complexes with the human enzyme. The best result reported in this work was the pesticide PM22, which presented an average Gibbs free energy of -775.1 kJ.mol-1 for the complex formed with the enzyme AaAChE and an average Gibbs free energy of -468.52kJ.mol-1 for the complex formed with the HssAChE enzyme. Those results and analyzes by molecular dynamics of the PM22, PROP2 and PROP3 proposals may be useful for the development of new pesticides that are selective for mosquitoes of the Aedes aegypti genus and that present less toxic to humans.