Repellency and Toxicity of Vapor-Active Benzaldehydes against Aedes aegypti

Chemical screening efforts recently found that 3-phenoxybenzaldehyde, a breakdown product of alpha-cyano pyrethroids, was a potent spatial repellent against Aedes aegypti mosquitoes in a glass tube repellency assay. In order to characterize this molecule further and identify structure–activity relationships, a set of 12 benzaldehyde analogues were screened for their repellency and toxicity in vapor phase exposures at 100 μg/cm². Dose–response analyses were performed for the most active compounds in order to better characterize their repellent potency and toxicity compared to those of other commercially available toxicants. The three most toxic compounds (LC₅₀ values) were 3-chlorobenzaldehyde (CBA) (37 μg/cm²), biphenyl-3-carboxaldehyde (BCA) (48 μg/cm²), and 3-vinylbenzaldehyde (66 μg/cm²), which makes them less toxic than bioallethrin (6.1 μg/cm²) but more toxic than sandalwood oil (77 μg/cm²), a repellent/toxic plant essential oil. The most repellent analogues with EC₅₀ values below 30 μg/cm² were 3-phenoxybenzaldehyde (6.3 μg/cm²), isophthalaldehyde (23 μg/cm²), BCA (17 μg/cm²), and CBA (22 μg/cm²), which makes them about as active as N,N-diethyl-3-methylbenzamide (25.4 μg/cm²). We further investigated the activity of a select group of these benzaldehydes to block the firing of the central nervous system of A. aegypti larvae. Compounds most capable of repelling and killing mosquitoes in the vapor phase were also those most capable of blocking nerve firing in the larval mosquito nervous system. The results demonstrate that benzaldehyde analogues are viable candidate repellent and insecticidal molecules and may lead to the development of future repellent and vapor toxic vector control tools.