Acylated 1,3-Aminopropanols as Repellents against Bloodsucking Arthropods

Starting from a set of known repellent compounds, a general structural framework with high probability for repellent activity was developed by molecular modelling techniques. Synthesis, structure–biological activity relationships of acylated 1,3-aminopropanols on the yellow fever mosquito Aedes aegypti and the properties and activity of the new development candidate compound KBR 3023 on Ae. aegypti, the malaria mosquito Anopheles stephensi, the common house mosquito Culex quinquefasciatus and the stable fly Stomoxys calcitrans are described. The sensory effect of KBR 3023 and deet has been studied in behavioural and neurophysiological investigations on Ae. aegypti and the American cockroach Periplaneta americana. The compounds clearly reduce or even eliminate the approach behaviour towards attractants like host odours or sexual pheromones. Electrophysiological studies on the insects' olfactory receptor organs reveal that certain cell types, which are not involved in perception of the attractive odorants, respond to deet and/or KBR 3023. As soon as one of the compounds is presented together with an attractant, a new input is active in the brain, which adds to the input from other receptors activated by the attractant. This new overall pattern clearly differs from that elicited by the attractant, so that the insect is no longer able to detect the latter. The specificity and mode of action of KBR 3023 was investigated by experiments exploring second-messenger responses elicited in antennal preparations of male P. americana. KBR 3023 induced a rapid increase in the concentration of inositol triphosphate in a dose-dependent and tissue-specific manner; other second-messenger systems were not affected. These observations suggest that KBR 3023 may act via subsets of G-protein-coupled receptors in sensory neurones.