|Bernier, Ulrich - Uli|
|Linthicum, Kenneth - Ken|
Submitted to: Proceedings of the National Academy of Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/1/2008
Publication Date: 5/27/2008
Citation: Katritzky, A.R., Wang, Z., Slavov, S., Tsikolia, M., Dobchev, D., Akhmedov, N.G., Hall, C.D., Bernier, U.R., Clark, G.G., Linthicum, K.J. Synthesis and bioassay of improved mosquito repellents predicted from chemical structure. Proceedings of the National Academy of Sciences of the USA. 105(21):7359-7364. 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 to predict how well a repellent will perform based on its chemical structure. The study was performed on chemicals that are similar in structure to the well known mosquito repellent DEET (N,N-diethyl-m-toluamide). Some of the chemicals came from the sixty year historical archives of tested repellents at the laboratory in Gainesville and some of the chemicals were novel, having been designed based upon these studies. A total of 34 chemicals were tested as repellents in a screening assay. The screening assay involved soaking a cloth with repellent, drying the cloth, and then testing the number of days that the repellent prevented mosquito bites through the cloth when the cloth was worn over the arm of a human volunteer. Over a third of the chemicals lasted at least twice as long as DEET in these tests. The results from these tests were then used to produce a model of a “good” repellent based on the chemical structure. The models were found to be very accurate in their ability to predict good repellents.
Technical Abstract: Mosquito repellency data on acylpiperidines derived from the US Department of Agriculture archives were modeled using molecular descriptors calculated by CODESSA pro software. An artificial neural network model was developed for the correlation of these archival results and used to predict the repellent activity of novel compounds of similar structures. A series of 34 promising N-acylpiperidine mosquito repellent candidates (4a–4q') were synthesized by reactions of acylbenzotriazoles 2a–2p with piperidines 3a–3f. Compounds (4a-4q’) were screened as topically applied mosquito repellents by measuring the duration of repellency after application to cloth patches worn on the arms of human volunteers. A majority of the compounds that were evaluated repelled mosquitoes three times longer than that of N,N-diethyl-m-toluamide (DEET), the most widely used repellent throughout the world. The newly measured durations of repellency were utilized to obtain a superior correlation equation relating mosquito repellency to molecular structure.