The control of insect pests and the need for increased food production due to the world population growth, together with the environmental issues associated to synthetic pesticides, has stimulated the development of new and “greener” alternatives, based on natural compounds. Eugenol is a natural compound that is the major component of clove oil. It has demonstrated antimicrobial and antioxidant activity, being also a powerful insecticide. Recently, new eugenol derivatives have been developed, with some molecules displaying increased insecticide activity. One of the difficulties associated to the rational development of new eugenol derivatives with enhanced insecticidal activity lies in the lack of knowledge of the specific protein target responsible for its activity and to the binding conformation of these molecules.

Here, we report the application of an integrated molecular modelling - inverted virtual screening protocol of a collection of eugenol derivatives with confirmed insecticide activity against a molecular library of protein targets typically associated with the insecticide activity of natural compounds. The protocol included 6 different scoring functions from popular docking software alternatives. The results consistently show a marked preference for interaction of the eugenol derivatives with the odorant binding proteins (OBPs) in insect species. Interestingly, OBPs have been regarded as promising targets in the insect periphery nerve system for environmentally-friendly approaches in insect pest management. The present results provide clues for the rational development of new eugenol derivatives as bioinsecticides targeting OBPs.