Selectivity of new molecules across insect orders: in silico and in vivo evaluations

Insecticides play a major role in pest management strategies. However, the continued use of these products elicits pest resistance and their insufficient biochemical selectivity may affect useful insects and vertebrates. For decades these challenges have fueled efforts to develop novel insecticides that – for some time – overcome resistance and show some degree of selectivity. Such advances, at first largely based on a shotgun approach or trial and error, have relied increasingly on the modification of insecticidal natural products, becoming more rational over the years. We are currently developing a heuristic methodology that will lead to improved design, new syntheses, testing, and the discovery of one or more novel families of compounds with the potential to selectively target particular groups of harmful insects. Considering the known amino acid sequences of specific receptors from different insect orders we have built computational models of different proteins in order to rationalize the interactions of new insecticides and Imidacloprid. Here we present experimental and in silico results on Myzus persicae and Drosophila melanogaster as model systems. Our findings improve our understanding on the specific interactions between proteins and target specific insecticides, and give us new insights about structure-activity relationships for the design of new selective insecticides. Grants: COPEC-UC.2013.R33, VRI-PUC11/2013