Semi-synthetic cinnamodial analogues: Structural insights into the insecticidal and antifeedant activities of drimane sesquiterpenes against the mosquito Aedes aegypti
| Autor: | Sijin Wu, Megha Kalsi, Peter M. Piermarini, Preston K. Manwill, Harinantenaina L. Rakotondraibe, Xiaolin Cheng, Erick J. Martinez Rodriguez |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Models Molecular Insecticides Life Cycles Mosquito Control Protein Conformation RC955-962 Disease Vectors medicine.disease_cause Toxicology Pathology and Laboratory Medicine Mosquitoes Dengue fever chemistry.chemical_compound 0302 clinical medicine Larvae Aedes Arctic medicine. Tropical medicine Medicine and Health Sciences Chikungunya TRPA1 Cation Channel Larva Traditional medicine Molecular Structure Organic Compounds Eukaryota Cinnamosma fragrans Agriculture 3. Good health Insects Mosquito control Chemistry Infectious Diseases Physical Sciences Female Public aspects of medicine RA1-1270 Agrochemicals Research Article Arthropoda Infectious Disease Control 030231 tropical medicine Aedes aegypti Biology Aedes Aegypti Sesquiterpene 03 medical and health sciences Thiols medicine Animals Polycyclic Sesquiterpenes Aldehydes Toxicity fungi Organic Chemistry Public Health Environmental and Occupational Health Organisms Chemical Compounds Biology and Life Sciences Feeding Behavior medicine.disease biology.organism_classification Invertebrates Insect Vectors Species Interactions 030104 developmental biology chemistry Vector (epidemiology) Developmental Biology |
| Zdroj: | PLoS Neglected Tropical Diseases PLoS Neglected Tropical Diseases, Vol 14, Iss 2, p e0008073 (2020) |
| ISSN: | 1935-2735 |
| Popis: | 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. We recently discovered that cinnamodial, a unique drimane sesquiterpene dialdehyde of the Malagasy medicinal plant Cinnamosma fragrans, exhibited significant larval and adult toxicity to Ae. aegypti and was more efficacious than DEET–the gold standard for insect repellents–at repelling adult female Ae. aegypti from blood feeding. In this study several semi-synthetic analogues of cinnamodial 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 stable active analogues and to understand the importance of the 1,4-dialdehyde and the α,ß-unsaturated carbonyl in the observed bioactivity of cinnamodial against mosquitoes. This study represents the first investigation into the SAR of cinnamodial as an insecticide and antifeedant against the medically important Ae. aegypti mosquito. Author summary Aedes mosquitoes are the primary carriers of Zika, dengue, chikungunya, and yellow fever viruses around the globe. Given the emergence of insecticide-resistance in this genus and unprecedented ‘globalization’ of mosquito-borne viruses, new chemicals to control these mosquitoes (e.g., insecticides, repellents) are urgently needed. In the continuation of our search for new and safe natural product derived insecticides, we generated semi-synthetic derivatives of cinnamodial (CDIAL), previously identified as an insect antifeedant, repellent and insecticide, to give insights into the important features of the molecule that can contribute to the observed activities. Since the antifeedant and repellent activity of CDIAL are found to be mediated by modulation of a sensory receptor (TRPA1) in the mosquito, we developed a structural model to understand how CDIAL interacts with TRPA1 and to explain the difference in activities of CDIAL and the prepared derivatives. Our findings aid in the development of plant-derived insecticides to control the Ae. aegypti mosquito and justify continued efforts using TRPA1 as a target for new mosquito repellents. |
| Databáze: | OpenAIRE |
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