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Aedes aegypti mosquitoes transmit dengue and Zika fever, critical problems in Public Health. Chemical control remains an important strategy to decrease mosquito population. 3-Hydroxykynurenine transaminase (HKT) is a detoxification enzyme that converts 3-hydroxykynurenine (unstable compound) into xanthurenic acid (nontoxic molecule). 1,2,4-Oxadiazole derivatives showed larvicidal activity with evidence of inhibiting HKT in Ae. aegypti mosquitoes. Therefore, we investigated the role of HKT as molecular target of 1,2,4-oxadiazole derivatives. The cloning and expression of Aedes aegypti HKT gene and recombinant protein purification were performed in a final yield of 30 mg.L-1. To assess enzyme kinetics and inhibition profile, a fast and cheap methodology was developed based on detection of xanthurenic acid-Fe3+ complex at 570 nm. The eleven synthesized and new 1,2,4-oxadiazoles showed IC50 between 42 and 294 μM, behaving as noncompetitive inhibitors. We are now performing computational simulations to identify groups involved in enzyme-inhibitor interactions.
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