Fundamental Mechanisms of Mosquito Attraction and Inhibition, 01-R9696Printer Friendly Version
Inclusive Dates: 04/01/07 12/29/09
Background - A chief hurdle in developing new insect repellents is the costly, time-consuming pre-market testing and approval process. Naturally occurring compounds or their derivatives may have an easier approval route. To reduce the cost of searching for novel natural compounds SwRI researchers applied tools of virtual drug discovery to the problem of mosquito repellents.
Approach - Discovery of novel mosquito inhibitors by virtual screening was accomplished using quantitative-structure-property-relationship (QSPR) methods. A QSPR is an equation that relates certain selected molecular descriptors to a measured property, in this case inhibition of mosquito attraction to bait (lactic acid). From inhibition data on several hetrocyclic amines obtained from the United States Department of Agriculture as part of this project, a training set was developed and a QSAR model constructed. Quantum chemical calculations were used to generate descriptors of each molecule.
Accomplishments - After the QSAR equation was developed and validated, molecular descriptors were calculated for approximately 17,000 chemical compounds. This library was screened for mosquito inhibition. From approximately 17,000 compounds, 62 were selected for tests on live mosquitoes. Of those selected, 14 compounds are strong or moderate repellents. Several chemical compounds, including two FDA-approved food additive compounds and a fragrance additive, were found to inhibit mosquito attraction. The inhibiting abilities have been confirmed in actual olfactometer tests on ades aegypti mosquitoes by the USDA. Future work in this area could involve more detailed receptor-level screening of novel repellents discovered in this study, to determine if a pharmacophore could be developed. SwRI has a sensilium receptor assay that could be used for this work. Several compounds discovered in this study could be candidates for controlled-release formulations for mosquito control. FDA-approved flavoring and fragrance agents are especially promising for commercialization. Discussions are ongoing with USAMRID, USDA, and the U.S. Army Pest Control Board regarding potential development of controlled-release formulations of these compounds.