Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 2/7/2018
Publication Date: 2/15/2018
Citation: Tsikolia, M., Bernier, U.R., Jiang, S., Yang, L., Cuba, I., O'Reilly, E.E., Agramonte, N.M., Linthicum, K., Bloomquist, J.R. 2018. Fluorine-Containing novel spatial and contact repellents. Meeting Abstract. pg. 1.

Interpretive Summary:

Technical Abstract: Mosquito-transmitted diseases such as malaria, dengue, and yellow fever, result in thousands of human deaths yearly. Climate change and global warming can enhance the vectorial capacity, and the temporal and spatial distribution of mosquito populations. To find more effective tools for mosquito and disease control, we focus on the development of new repellents and insecticides to prevent mosquito bites and reduce disease risk to humans. We have synthesized 79 trifluoromethylphenyl amides in four successive stages. Each successive generation was chosen based on active structures of the previous generation. These compounds were evaluated for repellent activity against female Aedes aegypti. Six compounds were contact repellents and up to 10 compounds were spatial repellents, equal to or exceeding the activity of DEET. Several trends were observed between structural features and activities of the compounds. For contacts repellent activity, e.g., amides with -CF2CF3 moiety at a carbonyl carbon were more likely to have higher repellent activity than others. Adding chlorine to the para- position of the amide group in 3,4,5-trichlorophenyl amides decreased the repellent activity compared to the analogous compounds without chlorine at para- position (3, 5-dichlorophenyl amides). There was some correlation observed (r2 ~ 0.4) between vapor pressure and the minimum effective dose (MED) of repellency of the amides and no or weak correlation between MED of repellency and lipophilicity or Pka values. The LogP for most active compounds range from ~ 2.5-4. Salicylic acid esters and 2-Trifluoromethylbenzoic acid esters were more active spatial repellents than DEET; derivatives with a shorter alkyl chain were slightly better repellents than those with longer chains. 4-carbamic acid methyl esters were comparable or better than DEET. Four derivatives of 2-Trifluoromethyphenyl amides, also, showed better or comparable to DEET activity. There was a weaker correlation between vapor pressure vs EC50 ((r2 ~ 0.20) for Aedes/OR than Aedes/PR ((r2 ~ 0.45). These studies lead to the discovery of novel structures that could result in the discovery of new compounds with repellent activity.