Location: Mosquito and Fly ResearchTitle: Promising Aedes aegypti repellent chemotypes identified through integrated QSAE, virtual screening, synthesis, and bioassay Author
|Bernier, Ulrich - Uli|
|Linthicum, Kenneth - Ken|
Submitted to: PLoS One
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/25/2013
Publication Date: 9/6/2013
Citation: Oliferenko, P.V., Oliferenko, A.A., Poda, G.I., Osolodkin, D.I., Pillai, G.G., Bernier, U.R., Tsikolia, M., Agramonte, N.M., Clark, G.G., Linthicum, K., Katritzky, A.R. 2013. Promising Aedes aegypti repellent chemotypes identified through integrated QSAE, virtual screening, synthesis, and bioassay. PLoS One. 8(9):e64547. 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 and Moscow State University, Russia, have used molecular modeling to compare repellents and predict new repellents based on chemical structure. The well known repellent DEET (N,N-diethyl-m-toluamide) and approximately 70 other repellent compounds were used to develop the model which is based on the odorant binding protein 1 (OBP1) for the Aedes aegypti mosquito. It is believed that OBP1 is involved in the action of repellent chemicals such as DEET. Most of these chemicals came from research conducted in the past 5 years. Repellency values were based on the minimum effective dosage needed to prevent mosquitoes from biting. The results of this study confirmed the findings of the behavioral assay by demonstrating good agreement between predicted repellency and experimental repellency. The results of this research will be useful to scientists developing novel or improved repellents for protection from mosquito bites.
Technical Abstract: Molecular field topology analysis, scaffold hopping, and molecular docking were used as complementary computational tools for the design of repellents for Aedes aegypti, the insect vector for yellow fever, West Nile fever, and dengue fever. A large number of analogues were evaluated by virtual screening with Glide molecular docking software. This produced several dozen hits, which were either synthesized or procured from commercial sources to form a behavioural bioassay, which resulted in a few highly active chemicals (in terms of minimum effective dosage) as viable candidates for further hit-to-lead and lead optimization effort.