The enzyme 3-hydroxykynurenine transaminase as potential target for 1,2,4-oxadiazoles with larvicide activity against the dengue vector Aedes aegypti |
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Authors: | Vanessa S Oliveira Cecília Pimenteira Diana CB da Silva-Alves Laylla LL Leal Ricardo AW Neves-Filho Daniela MAF Navarro Geanne KN Santos Kamilla A Dutra Janaína V dos Anjos Thereza A Soares |
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Institution: | Department of Fundamental Chemistry, Federal University of Pernambuco, Recife 50740-560, Brazil |
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Abstract: | 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. |
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Keywords: | Larvae pigmentation Insecticide Molecular docking calculations 4-(2-Aminophenyl)-4-oxobutanoic acid |
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