Pyrethroid-derived acids and alcohols: bioactivity and synergistic effects on mosquito repellency and toxicity

Authors: YANG, LIU - University Of Florida; RICHOUX, GARY - University Of Florida; NORRIS, EDMUND - University Of Florida; Cuba, Ingeborg; JIANG, SHIYAO - University Of Florida; COQUEREL, QUENTIN - University Of Florida; Linthicum, Kenneth - Ken; BLOOMQUIST, JEFFREY - University Of Florida

Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/14/2020
Publication Date: 2/14/2020
Citation: Yang, L., Richoux, G.M., Norris, E., Cuba, I., Jiang, S., Coquerel, Q., Linthicum, K., Bloomquist, J.R. 2020. Pyrethroid-derived acids and alcohols: bioactivity and synergistic effects on mosquito repellency and toxicity. Journal of Agricultural and Food Chemistry. https://doi.org/10.1021/acs.jafc.9b07979.
DOI: https://doi.org/10.1021/acs.jafc.9b07979

Interpretive Summary: Mosquitoes are the primary vectors of malaria parasites, dengue fever, chikungunya, yellow fever, and Zika virus. Over 400,000 deaths from these diseases are reported every year, and infection rates are likely to grow, especially for dengue, and malaria. Appropriate and safe use of topical insect repellents, such as DEET (N,N-diethyl-m-toluamide) and pyrethroids, play an important role in preventing disease transmission by interrupting mosquito host-seeking behaviors. However, the development of new spatial repellents represent a novel method to preven mosquito bites without the repellent coming in contact with human skin. In this study, we describe the discovery that the acid components of pyrethroid insecticides can synergize pyrethroids and enhance their spatial repellent activity. Additionally, these newly synergized spatial repellents appear to repel otherwise pyrethroid-resitant mosquitoes.

Technical Abstract: Pyrethroids are one of the most commonly used insecticides, and their acid and alcohol constituents, esterase degradation products, are typically considered to be inactive. In this study, it was found that several pyrethroid derived acids had spatial repellent activity greater than DEET, were often more active spatially than the parent pyrethroids, and exhibited little resistance in the pyrethroid-resistant Puerto Rico strain of Aedes aegypti mosquitoes. Further investigation showed that these acids can synergize the spatially repellent activity of not only contact repellent standards (e.g., DEET, 2-undecanone, etc.) but also other pyrethroid acids, pyrethroid alcohols, an aldehyde derived from a pyrethroid alcohol, and the parent pyrethroids themselves. The synergism of the pyrethroid acids is expressed as both increased spatial repellency and vapor toxicity, as well as bite protection of contact repellents in a human arm assay. Electrophysiological studies confirmed that pyrethroid acids were detected by antennae and there was no resistance to olfactory sensing of these acids in antennae from the Puerto Rico strain of Ae. aegypti. The available data suggest that the pyrethroid acids have a different mode of action than the parent pyrethroids, unrelated to the voltage-sensitive sodium channel. The results highlight the potential of pyrethroid acids to be useful in future repellent formulations, due to their intrinsic bioactivity and lack of cross-resistance on a pyrethroid-resistant strain of mosquito.