Submitted to: Chemistry and Biodiversity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/18/2008
Publication Date: 2/2/2009
Citation: Cantrell, C.L., Klun, J.A., Pridgeon, Y.W., Becnel, J.J., Green Iii, S., Fronczek, F.R. 2009. Structure-Activity Relationship Studies on the Mosquito Toxicity and Biting Deterrency of Callicarpenal Derivatives. Chemistry and Biodiversity. 6:447-458.
Interpretive Summary: In Mississippi, crushed leaves of the American beautyberry were placed under the harnesses of draft animals as a traditional means to protect the animals from flies and mosquitoes. Previous studies by some of the same authors resulted in the discovery of at least two of compounds, callicarpenal and intermedeol, the significantly repelled two species of mosquitoes and one species of ticks. The purpose of this study is to perform a structure-activity relationship study on both the mosquito biting deterrency and mosquito toxicity of synthetic analogs of callicarpenal. Callicarpenal is currently being investigated by the United States Department of Agriculture’s Agricultural Research Service (USDA-ARS) as a possible alternative to commercially available natural and synthetic based insect repellents. Discussed in this paper are chemical/synthetic modifications performed to callicarpenal including oxidations and reductions of the C-12 aldehyde to its corresponding acid or alcohol, complete reduction of the C-3 olefin, epoxidation of the C-3 olefin, and various methyl ester and acetate products. Combinations of the above modifications will also be discussed as well as their effects on both Ae. aegypti biting-deterrency and toxicity.
Technical Abstract: Callicarpenal (13,14,15,16-tetranor-3-cleroden-12-al) has previously demonstrated significant mosquito bite-deterring activity against Aedes aegypti and Anopheles stephensi in addition to repellent activity against host-seeking nymphs of the blacklegged tick, Ixodes scapularis. In the present study, structural modifications were performed on callicarpenal in an effort to understand the functional groups necessary for maintaining and/or increasing its activity and to possibly lead to more effective insect control agents. All modifications in this study targeted the C-12 aldehyde or the C-3 olefin functionalities or combinations thereof. Mosquito biting deterrency appeared to be influenced most by C-3 olefin modification as evidenced by catalytic hydrogenation that resulted in a compound having significantly less effectiveness than callicarpenal at a test amount of 25 nmoles/cm2. Oxidation and/or reduction of the C-12 aldehyde did not diminish mosquito biting deterrency, but at the same time, none of the modifications were more effective than callicarpenal in deterring mosquito biting. Toxicities of synthesized compounds towards Ae. aegypti ranged from an LD50 of 2.36 ug to 40.11 ug per mosquito. Similarly, LD95 values ranged from a low of 5.59 ug to a high of 104.9 ug.