Partridge, FA;
Poulton, BC;
Lake, MAI;
Lees, RA;
Mann, H-J;
Lycett, GJ;
Sattelle, DB;
(2021)
Actions of Camptothecin Derivatives on Larvae and Adults of the Arboviral Vector Aedes aegypti.
Molecules
, 26
(20)
, Article 6226. 10.3390/molecules26206226.
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Abstract
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 EC_{50} 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 topoisomerase I, have known activity against several agricultural pests, and are also approved for the treatment of several cancers. Crucially, they can inhibit Zika virus replication in human cells, so there is potential for dual targeting of both the vector and an important arbovirus that it carries.
| Type: | Article |
|---|---|
| Title: | Actions of Camptothecin Derivatives on Larvae and Adults of the Arboviral Vector Aedes aegypti |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3390/molecules26206226 |
| Publisher version: | https://doi.org/10.3390/molecules26206226 |
| Language: | English |
| Additional information: | © 2021 MDPI. This is an open access article distributed under the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). |
| Keywords: | insecticide; mosquito; Aedes; camptothecin; vector; rubitecan |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10136769 |
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