Discovery of Repellents from Natural Products

Natural products are an ideal source of chemicals for topical application to human skin, and can be a means of personal protection from the bites of mosquitoes and other arthropods. This report covers a diverse array of natural compounds, and includes descriptions of observed correlations between chemical properties and repellency. Repellent efficacy is determined by a 'cloth-patch' assay, which involves human volunteers testing chemically-treated cloth in cages of adult female mosquitoes. Known concentrations of chemical are applied to cloth and the treated cloth is affixed on the arm of a volunteer. The volunteer inserts the clothed arm into a cage of adult female mosquitoes to determine if they will land and bite through the treated cloth. The Minimum Effective Dosage (MED) is determined as the threshold concentration at which 1% of the mosquitoes bite through the treated cloth. This standardized assay has been used to develop in silico models to predict the relationship between chemical and structural properties, as well as the repellent performance. This report covers the past several years of our research, which has focused on natural products and essential oils extracted from plant species from different parts of the world. Structural indicators, such as the location of an oxygen or double bond in small molecules, have been found to predict repellency. The most potent natural repellent in our studies is carvacrol; however, this compound is also a skin irritant. Thymol, as well as terpinolene, alpha-terpineol, eugenol, and carvacrol methyl ether were also highly efficacious against Aedes aegypti. This work may lead to the discovery of derivatives of these compounds which possess both repellent efficacy and dermal safety.