QSAR modelling and structural aspects concerning synthetic heterocycles with larvicidal activity against Aedes aegypti

In this paper, we present a quantitative structure–activity relationships modelling for two series of heterocyclic synthetic compounds with larvicidal activity against Aedes aegypti . This is a vector of important disease around the tropical countries as dengue, zika, and chikungunya. The compounds corresponded to a set of 21 girgensohnine natural product analogues, containing an acetonitrile moiety, and 35 synthetic oxadiazoles and isoxazoles. The activities were expressed by IC 50 values in direct acetylcholinesterase inhibition (acetonitriles), as well as LC 50 in the observation of the larvae death (oxadiazoles/isoxazoles). Robust and predictive MLR (multiple linear regression) models were obtained after a variable selection procedure, using the OPS (ordered predictors selector) algorithm and Dragon descriptors. We highlighted important molecular descriptors related to the activity of each class, in order to predict molecular modifications for the synthesis of new and more active compounds. We also provided an initial path for qualitative understanding of the activity spectrum in each of the class studied herein.