Synthesis and bioassay of improved mosquito repellents predicted from chemical structure

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[SIZE=+2] Synthesis and bioassay of improved mosquito repellents predicted from chemical structure[/SIZE] <nobr>Alan R. Katritzky<sup>

</sup><sup>,

</sup></nobr>, <nobr>Zuoquan Wang<sup>

</sup></nobr>, <nobr>Svetoslav Slavov<sup>

</sup></nobr>, <nobr>Maia Tsikolia<sup>

</sup></nobr>, <nobr>Dimitar Dobchev<sup>

</sup></nobr>, <nobr>Novruz G. Akhmedov<sup>

</sup></nobr>, <nobr>C. Dennis Hall<sup>

</sup></nobr>, <nobr>Ulrich R. Bernier^?</nobr>, <nobr>Gary G. Clark^?</nobr>, and <nobr>Kenneth J. Linthicum^?</nobr>
<sup>

</sup>Center for Heterocyclic Compounds, Department of Chemistry, 127 Chemistry Research Building, University of Florida, Gainesville, FL 32611-7200; and ^?United States Department of Agriculture, Agricultural Research Service, Center for Medical, Agricultural and Veterinary Entomology, Gainesville, FL 32608
Edited by Barry J. Beaty, Colorado State University, Fort Collins, CO, and approved April 1, 2008 (received for review January 18, 2008)

<!-- ABS --> Mosquito repellency data on acylpiperidines derived from theU.S. Department of Agriculture archives were modeled by usingmolecular descriptors calculated by CODESSA PRO software. Anartificial neural network model was developed for the correlationof these archival results and used to predict the repellentactivity of novel compounds of similar structures. A seriesof 34 promising N-acylpiperidine mosquito repellent candidates(4a?4q') were synthesized by reactions of acylbenzotriazoles2a?2p with piperidines 3a?3f. Compounds (4a?4q')were screened as topically applied mosquito repellents by measuringthe duration of repellency after application to cloth patchesworn on the arms of human volunteers. Some compounds that wereevaluated repelled mosquitoes as much as three times longerthan N,N-diethyl-m-toluamide (DEET), the most widely used repellentthroughout the world. The newly measured durations of repellencywere used to obtain a superior correlation equation relatingmosquito repellency to molecular structure.

[SIZE=-1]N-acylpiperidine | quantitative structure?activity relationship | CODESSA PRO | artificial neural network | Aedes aegypti[/SIZE]

<hr align="left" noshade="noshade" size="1" width="50%"> <!-- FN --> <!-- null --> Author contributions: A.R.K., S.S., D.D., U.R.B., G.G.C., andK.J.L. designed research; Z.W., M.T., N.G.A., U.R.B., G.G.C.,and K.J.L. performed research; S.S., D.D., and C.D.H. analyzeddata; and A.R.K., Z.W., S.S., M.T., C.D.H., U.R.B., G.G.C.,and K.J.L. wrote the paper. <!-- null --> The authors declare no conflict of interest.
<!-- null --> This article is a PNAS Direct Submission.
<!-- null --> This article contains supporting information online at www.pnas.org/cgi/content/full/0800571105/DCSupplemental.
<!-- null --> <sup>

</sup>To whom correspondence should be addressed. E-mail: katritzky@chem.ufl.edu<script type="text/javascript"><!-- var u = "katritzky", d = "chem.ufl.edu"; document.getElementById("em0").innerHTML = '<a href="mailto:' + u + '@' + d + '">' + u + '@' + d + '<\/a>'//--></script>
? 2008 by The National Academy of Sciences of the USA



http://www.pnas.org/cgi/content/abstract/105/21/7359