Model to design insecticides against Aedes aegypti using in silico and in vivo analysis of different pharmacological targets.

Compounds having insecticidal activity can be used to control Aedes aegypti mosquitoes, a major worldwide vector, and several plants have a source of such molecules. A principal component analysis (PCA) was carried out to determine the criterion to select larvicidal metabolites. The insecticidal activity of seven selected metabolites by PCA was validated by determining its lethal concentrations 50 (LC50) by probit analysis. Six of the seven evaluated molecules presented LC50 values <100 ppm. The effects of these six molecules on acetylcholinesterase and the respiratory chain complexes of the mitochondria of Ae. aegypti were evaluated. Four metabolites presenting the highest inhibition effects on these targets were mixed in 11 different combinations, and the percentage of mortality of each mixture on Ae. aegypti larvae were determined. Secondary metabolites such as geranyl acetate, α-humulene, β-caryophyllene, geraniol, nerol, and n-octanol presented LC50 values under 100 ppm (44, 41, 48, 84, 87, and 98 ppm, respectively), whereas 1,8-cineole presented a LC50 value of 183 ppm. We found that, geranyl acetate, α-humulene, β-caryophyllene, nerol, n-octanol, and geraniol inhibited at least one of the six targets with an efficiency between 25 and 41%. Overall, the evaluation of the different mixtures revealed a synergistic effect between geranyl acetate and geraniol, and an antagonistic effect between α-humulene and β-caryophyllene compounds.