Autor(es): Oliveira Vanessa S,Pimenteira Cecília,da Silva-Alves Diana C B,Leal Laylla L L,Neves-Filho Ricardo A W,Navarro Daniela M A F,Santos Geanne K N,Dutra Kamilla A,dos Anjos Janaína V,Soares Thereza A

Resumo: The mosquito Aedes aegypti is the vector agent responsible for the transmission of yellow fever and dengue fever viruses to over 80 million people in tropical and subtropical regions of the world. Exhaustive efforts have lead to a vaccine candidate with only 30% effectiveness against the dengue virus and failure to protect patients against the serotype 2. Hence, vector control remains the most viable route to dengue fever control programs. We have synthesized a class of 1,2,4-oxadiazole derivatives whose most biologically active compounds exhibit potent activity against Aedes aegypti larvae (ca. of 15 ppm) and low toxicity in mammals. Exposure to these larvicides results in larvae pigmentation in a manner correlated with the LC50 measurements. Structural comparisons of the 1,2,4-oxadiazole nucleus against known inhibitors of insect enzymes allowed the identification of 3-hydroxykynurenine transaminase as a potential target for these synthetic larvicides. Molecular docking calculations indicate that 1,2,4-oxadiazole compounds can bind to 3-hydroxykynurenine transaminase with similar conformation and binding energies as its crystallographic inhibitor 4-(2-aminophenyl)-4-oxobutanoic acid.

Palavras-Chave: Larvae pigmentation; Insecticide; Molecular docking calculations; Malaria vector Anopheles gambiae; 4-(2-Aminophenyl)-4-oxobutanoic acid

Imprenta: Bioorganic & Medicinal Chemistry, v. 21, n. 22, p. 6996-7003, 2013

Identificador do objeto digital: 10.1016/j.bmc.2013.09.020

Descritores: Aedes aegypti - Molecular Structure ; Aedes aegypti - Protein synthesis ; Aedes aegypti - virus ; Aedes aegypti - Larvicide ; Aedes aegypti - Transmission ; Aedes aegypti - Vaccine ; Aedes aegypti - Dengue

Data de publicação: 2013

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