Location: Mosquito and Fly Research Unit
Title: Novel carboxamides as potential mosquito reprellents. Authors
|Katritzky, Alan -|
|Wang, Zuoquan -|
|Slavav, Svetoslav -|
|Dobchev, Dimitar -|
|Hall, C. -|
Submitted to: Journal of Medical Entomology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 12, 2010
Publication Date: March 27, 2010
Citation: Katritzky, A.R., Wang, Z., Slavov, S., Dobchev, D.A., Hall, C.D., Tsikolia, M., Bernier, U.R., Elejalde, N.M., Clark, G.G., Linthicum, K.J. 2010. Novel carboxamides as potential mosquito repellents. Journal of Medical Entomology. 47(5):924-938. DOI: 10.1603/ME09284. Interpretive Summary: Scientists at the USDA-ARS, Center for Medical, Agricultural, and Veterinary Entomology in Gainesville, FL, in collaboration with scientists from the University of Florida, have studied mosquito repellents by making a model to predict new compounds that will also protect from mosquito bites. The compounds used in the model have a structure that is similar to the well known repellent DEET (N,N-diethyl-m-toluamide). The repellency data for these chemicals came from the ARS archives which contain 60 years of data. All of the 38 chemicals that were predicted to be good repellents were made so that they could then be tested. The screening tests involved soaking a cloth with a chemical, drying the cloth, and then wearing the cloth above the skin of a human volunteer. Both the number of consecutive days that the chemical prevented mosquito bites through the cloth and the amount of chemical needed to prevent mosquitoes from biting through was measured. One of the chemicals lasted between 2 and 3 times as long as DEET, depending on the amount of this compound on the cloth. Another of the compounds protected the skin from bites through the cloth at a lower concentration than DEET.
Technical Abstract: A model was developed using 167 carboxamide compounds, from the US Department of Agriculture archival database, that were tested as arthropod repellents over the past 60 years. An artificial neural network utilizing CODESSA PRO descriptors was used to construct a Quantitative Structure-Activity Relationship (QSAR) model for prediction of novel mosquito repellents. By correlating the structure of these carboxamides with Complete Protection Time (CPT), a measure of repellency based on duration, 34 carboxamides were predicted as candidate mosquito repellents. There were 4 additional compounds selected on the basis of their structural similarity to those predicted. The compounds were synthesized either by reaction of 1-acylbenzotriazoles with secondary amines or by reaction of acid chlorides with secondary amines in the presence of sodium hydride. The biological efficacy was assessed by duration of repellency on cloth at two dosages (25 and 2.5 µmol/cm2) and by the Minimum Effective Dosage (MED) to prevent Aedes aegypti (L.) (Diptera: Culicidae) bites. One compound, (E)-N-cyclohexyl-N-ethyl-2-hexenamide, was superior to N,N-diethyl-3-methylbenzamide (deet) at both the high dosage (22 d vs. 7 d for deet) and low dosage (5 d vs. 2.5 d for deet). Only one of the carboxamides, hexahydro-1-(1-oxohexyl)-1H-azepine had a MED that was equivalent or slightly better than that of deet (0.033 µmol/cm2 vs. 0.047 µmol/cm2).