Modelagem de tetraidroquinolinas: efeito larvicida e adulticida em Aedes aegypti

• Ano de defesa: 2017
• Autor(a) principal: Giacoppo, Juliana de Oliveira Silva
• Tipo de documento: Tese
• 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: Receptor de ecdisona; Acetilcolinesterase; Modelagem por homologia; Docking; Dinâmica molecular; Ecdysone receptor; Acetylcholinesterase; Homology modeling; Molecular dynamics; Química
• Link de acesso: http://repositorio.ufla.br/jspui/handle/1/12773

Mosquito-borne diseases (arboviruses) have been made constant threats in tropical regions. While there is no valid vaccine against the virus of diseases such as dengue, zika, chikungunya and mayaro fever the only form of prevention existing is the control of the mosquitoes transmitting Aedes aegypti and/or Aedes Albopictus. The search for new insecticides, associated with the elimination of possible A. aegypti breeding sites, is of fundamental importance in the fight against this vector. It is necessary to obtain compounds that are more effective, less stable in the environment as well as less toxicity to humans. In addition, the search for new molecular targets is also essential. This work was carried out in two stages: first, a study was carried out on the larvicidal and/or adulticidal action of some tetrahydroquinolines derivatives already tested against Aedes aegypti. In this case, we studied the interaction of this class of compounds in the ecdysone receptor (AaEcR) and also in the BK channel of the mosquito. From our theoretical findings, new and promising compounds against Aedes aegypti have been designed. The second stage is devoted to interaction of these same compounds (already tested and those proposed) with acetylcholinesterase (AaAChE), analyzing the selectivity of these compounds to human enzyme (HssAChE). It is important to note that in both studies a theoretical methodology was applied using homology modeling, docking calculations and molecular dynamics simulations. Our findings show that the compound JG2, proposed in this work, has both larvicidal and adulticidal action, since it interacts well with the ecdysone receptor, with the BK channel as well as Aedes aegypti acetylcholinesterase. In addition, there is still greater selectivity to the mosquito enzyme than human acetylcholinesterase, which is important for toxicity of human. In line with that, our results indicate JG2 as a potential insecticide to be synthesized and tested against the Aedes aegypti mosquito.