Novel pyrethroid derivatives as effective mosquito repellents and repellent synergists

Authors: BLOOMQUIST, JEFFREY - University Of Florida; JIANG, SHIYAO - University Of Florida; Norris, Edmund; RICHOUX, GARY - University Of Florida; YANG, LIU - University Of Florida; Linthicum, Kenneth - Ken

Submitted to: Book Chapter
Publication Type: Book / Chapter
Publication Acceptance Date: 10/7/2021
Publication Date: 10/14/2021
Citation: Bloomquist, J., Jiang, S., Norris, E.J., Richoux, G., Yang, L., Linthicum, K. 2021. Novel pyrethroid derivatives as effective mosquito repellents and repellent synergists. In Corona, C., Debboun, M., Coats, J., editors, Advances in Arthropod Repellents. Elsevier Inc. p.19-32. https://doi.org/10.1016/B978-0-323-85411-5.00004-2.
DOI: https://doi.org/10.1016/B978-0-323-85411-5.00004-2

Interpretive Summary: Spatial repellents can repel mosquitoes which are exposed to only the vapor phase of compounds. Transfluthrin is a powerful spatial repellent that is very effective on repelling Aedes aegypti mosquitoes, the vector of Zika, dengue and chikungunya viruses. Spatial repellency screenings of individual acid and alcohol components of transfluthrin in high through-put small tube tests did not repel Ae. aegypti mosquitoes. However, the acid (TFA) did enhance the repellency of the corresponding alcohol, as well as the parent, transfluthrin. TFA could also synergize the neurophysiological actions of transfluthrin on tests conducted on the Central Nervous System of the fruit fly Drosophila melanogaster. TFA had no effect on non-synthetic pyrethroid repellents as imidacloprid, anthranilate and pyrazine. These studies were performed using a new high-throughput assay system that is simple, inexpensive, and rapid. Thus, it should serve as an ideal testing platform to further improve the efficacy of commercially available mosquito repellents, and also to investigate new cost-effective, low toxicity, and environmentally friendly compounds.

Technical Abstract: Vapor repellency assessments were made for mosquitoes in a recently described microassay. Fragment screens of the acid and alcohol of transfluthrin showed no effect of the acid (TFA) alone, but it did enhance the repellency of the corresponding alcohol. It was further observed that TFA could synergize the repellent effects of transfluthrin, as well as its neurophysiological actions on the larval Drosophila melanogaster CNS. In contrast, TFA had no effect on imidacloprid-dependent neuroexcitation, perhaps indicating a dual action with transfluthrin on the nerve membrane sodium channels. Anthranilate and pyrazine repellents were fast acting and were not synergized by TFA. Synthesis and repellency evaluation of the pure enantiomers of alpha-terpinyl isovalerate (alpha-TI) revealed a more slowly developing effect, but little EC50 difference from each isomer or the racemic mixture. Also, a-TI synergized the repellency of transfluthrin 10-fold, similar to that observed for TFA (7-fold). Taken together, these latter findings and the structural similarity of TFA to alpha-TI suggests they may work through common mechanisms and receptor(s), although experimental confirmation awaits further study.