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Identification and Optimization of New Leads for Malaria Vector Control.
Ottmar F Hueter1, Mark Hoppé2, Philip Wege3
1Insecticide Research Chemistry, Stein Research Centre, Schaffhauserstrasse, CH-4332 Stein, Switzerland. ottmar.hueter@syngenta.com.
Chimia
|October 26, 2016
Summary
New insecticide leads are crucial for malaria vector control due to widespread resistance. Researchers screened 30,000 compounds, identifying 12 viable leads, including novel candidates from herbicide and fungicide projects.
Area of Science:
- Entomology
- Medicinal Chemistry
- Public Health
Background:
- Insecticide resistance in malaria vectors, particularly to pyrethroids, threatens global malaria control efforts.
- The emergence and spread of resistance necessitate the development of novel vector control tools.
Purpose of the Study:
- To identify new chemical leads for malaria vector control by screening a large compound library.
- To discover compounds effective against insecticide-resistant mosquito populations.
Main Methods:
- A library of 30,000 compounds from the Syngenta corporate collection was screened using a novel platform.
- Compounds showing activity against Anopheles stephensi at ≤200 mg AI/liter were further evaluated.
- Lead optimization was performed on promising candidates, including diphenyl ether derivatives.
Main Results:
- Over 3,000 compounds (10%) demonstrated activity against Anopheles stephensi.
- Twelve viable leads for adult mosquito control were identified, with several originating from non-insecticide projects (herbicide, fungicide).
- Optimized compound 31 (cyano-pyridyl) showed good activity against various mosquito species, including resistant Anopheles, with minimal cross-resistance to dieldrin.
Conclusions:
- Novel chemical scaffolds, including those from herbicide and fungicide programs, can yield effective leads for malaria vector control.
- Compound 31 represents a promising candidate for controlling insecticide-resistant malaria vectors.
- Continued research into diverse chemical classes is vital for overcoming insecticide resistance challenges in malaria control.
