Molecules, Vol. 26, Pages 6226: Actions of Camptothecin Derivatives on Larvae and Adults of the Arboviral Vector Aedes aegypti

Molecules, Vol. 26, Pages 6226: Actions of Camptothecin Derivatives on Larvae and Adults of the Arboviral Vector Aedes aegypti Molecules doi: 10.3390/molecules26206226 Authors: Frederick A. Partridge Beth C. Poulton Milly A. I. Lake Rebecca A. Lees Harry-Jack Mann Gareth J. Lycett David B. Sattelle Mosquito-borne viruses including dengue, Zika, and Chikungunya viruses, and parasites such as malaria and Onchocerca volvulus endanger health and economic security around the globe, and emerging mosquito-borne pathogens have pandemic potential. However, the rapid spread of insecticide resistance threatens our ability to control mosquito vectors. Larvae of Aedes aegypti were screened with the Medicines for Malaria Venture Pandemic Response Box, an open-source compound library, using INVAPP, an invertebrate automated phenotyping platform suited to high-throughput chemical screening of larval motility. We identified rubitecan (a synthetic derivative of camptothecin) as a hit compound that reduced A. aegypti larval motility. Both rubitecan and camptothecin displayed concentration dependent reduction in larval motility with estimated EC50 of 25.5 ± 5.0 µM and 22.3 ± 5.4 µM, respectively. We extended our investigation to adult mosquitoes and found that camptothecin increased lethality when delivered in a blood meal to A. aegypti adults at 100 µM and 10 µM, and completely blocked egg laying when fed at 100 µM. Camptothecin and its derivatives are inhibitors of t...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research