Cinnamodial Analogues with Insecticidal and Antifeedant Activity to Control the Aedes aegypti Mosquito
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Date
2019-03
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Abstract
The Aedes aegypti mosquito serves as a major vector for viral diseases, such as dengue, chikungunya, and Zika, which are spreading across the globe and threatening public health. In addition to increased vector transmission, the prevalence of insecticide-resistant mosquitoes is also on the rise, thus solidifying the need for new, safe and effective insecticides to control mosquito populations. Plants have been an indispensable source of novel compounds possessing pharmacological activities relevant to public health. Pyrethroids, for instance, the most widely used insecticides in the United States and the only class approved for insecticide treated nets, are derived from natural pyrethrins isolated from the flowers of Chrysanthemum (Asteraceae).We recently identified that cinnamodial, a natural compound present in the bark of the Malagasy medicinal plant Cinnamosma fragrans Baill. (Canellaceae), exhibited significant larval and adult toxicity to Ae. aegypti and outperformed DEET – the gold standard for insect repellents – at repelling adult female Ae. aegypti from feeding. Cinnamodial belongs to the drimane sesquiterpene class of natural products and possesses two aldehyde functional groups located nearby each other, one of which being conjugated with a neighboring alkene, altogether, this α,β-unsaturated 1,4-dialdehyde moiety may play a critical role in eliciting insecticidal and antifeedant activity. In this study large quantities of cinnamodial were isolated from C. fragrans and several semisynthetic analogues were prepared to probe the structure-activity relationship (SAR) for larvicidal, adulticidal and antifeedant activity against Ae. aegypti. Initial efforts were focused on modification of the dialdehyde functionality to produce more active analogues and to understand the importance of the 1,4-dialdehyde and the α,ß-unsaturated carbonyl in the observed bioactivity of cinnamodial. This study represents the first investigation into the preliminary SAR of cinnamodial as an agent to control the spread of the medically important Ae. aegypti mosquito. Overall, we have identified several derivatives that confirm the importance of the α,ß-unsaturated carbonyl for mosquitocidal activity and the dialdehyde moiety for antifeedant activity. Additionally, two effective cinnamodial analogs have been identified which may serve as hit compounds for the generation of new Ae. aegypti larvicides and adulticides.
Description
Food, Agricultural, and Environmental Sciences (FAES): 2nd Place (The Ohio State University Edward F. Hayes Graduate Research Forum)
Keywords
cinnamodial, insecticidal, antifeedant, Aedes aegypti, mosquito, TRPA1
Citation
Preprint: Manwill, P.; Kalsi, M.; Wu, S.; Cheng, X.; Piermarini, P.; Rakotondraibe, H. L. Semi-Synthetic Cinnamodial Analogues: Structural Insights into the Insecticidal and Antifeedant Activities of Drimane Sesquiterpenes Against the Mosquito Aedes aegypti. bioRxiv 2019, 536961, DOI: 10.1101/536961.