Quantitative structure-toxicity relationships and molecular highlights about Aedes aegypti larvicidal activity of monoterpenes and related compounds

Abstract

Dengue is a viral tropical disease transmitted to humans via the bite of Aedes aegypti L. (Diptera: Culicidae) mosquitoes. Since there is no specific treatment for dengue, the only method for preventing virus transmission is to control its vector by using environmental management and chemical methods. In this work, we propose a quantitative structure-toxicity relationships study of 31 monoterpenes and structurally related compounds which are bioactive against Aedes aegypti larvae, aiming to identify structural features responsible for the compounds activity, with the goal to support lead optimization. After conformational studies and complete geometry optimizations in DFT level, 1666 descriptors were calculated by E-Dragon online platform. The ordered predictors selection algorithm selected nine important descriptors, which were reduced to three after further analysis (R8e+, MAXDN, nCt), considering twenty-four and seven compounds in training and test sets, respectively. The validation parameters of final MLR modeling for these variables were: R2 = 0.83; Q2loo = 0.77; Q2ext = 0.83, showing that a robust and predictive model was obtained.