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DWFP Toxicology Research to Develop Insecticides for Vector Control
Julia W. Pridgeon, PhDToxicologist/Molecular Biologist
02-14-07
Mosquito and Fly Research UnitCenter for Medical, Agricultural, and
Veterinary EntomologyUSDA-ARS, 1600 SW 23rd Drive
Gainesville, FL 32608
Research Objective
To discover and develop effective
chemical and molecular
insecticides for vector control
Military Relevance
♣ In military units, arthropod-borne diseases continue to be serious threats to deployed troops
♣ Chemical pesticides are the most effective way to control disease vectors, however, few products are available for military use
♣ Due to the nature of military operations, pesticides that can quickly and effectively eliminate arthropod vectors are highly desirable
Approach for the Development of Effective Chemical Insecticides
Registered Pesticides
Natural PlantChemicals
Plant ExtractsDesigner
Chemicals
USDA-ARS-NPURU
USDA-ARS-MFRU
NPURU & UF IRAC
High-Throughput Screen to find highly toxic chemical(Topical application; Aedes aegypti model)
Small Chamber Test and Field Evaluation
Topical Application
EasyAccurate
Small Amount Fast
Results of Studies on Chemical Insecticides
Registered Pesticides
Natural PlantChemicals
Plant Extracts
33
DesignerChemicals
USDA-ARS-NPURU
USDA-ARS-MFRU NPURU & UF IRAC
Pesticide LD50 (ug)
Fipronil 1.3 10-6
Permethrin 1.4 10-4
Spinosad 2.5 10-3
Bifenzate 4.25
19 26
AT-05-27-2(LD50 0.3ug)
123-1(LD50 = 0.4ug)
Bacopa monnieri (Water hyssop)Methanol Extract
LD50 125ug
33
LD50 =0.8ug
LD50 =2.1ug
LD50 =14.72ug
Summary on Studies of Chemical Insecticides
1)Screened 19 registered pesticides; several showed high insecticidal activity against Aedes aegypti
2)Screened 26 different natural plant chemicals (NPURU); two had relatively high toxicities
3) Screened 33 different plant extracts (MFRU), some had higher toxicity against mosquitoes than others
4) Screened 33 piperidines with different structures (UF and NPURU), 2-ethyl piperidines showed the highest toxicities against mosquito (in press in Journal of Medical Entomology)
Summary on Studies of Chemical Insecticides
Future Studies on Chemical Pesticides
1)Evaluate the toxicities of registered pesticides against different species of mosquitoes and other disease vectors
2)Select the best pesticide candidates for further evaluation in small chamber tests and field studies
3)Manipulate the structures of plant chemicals and evaluate their toxicities
4) Studies on toxicity of plant extracts will be continued (additional information by Dr. Quinn)
5) For structure-activity analysis, different classes of chemicals will be evaluated and the best ones chosen for further structure manipulation
Future Studies on Chemical Pesticides
Approach for the Developmentof Molecular Pesticides
(Aedes aegypti model)
Target Essential Target Essential PathwaysPathways Programmed Cell Death,
Mitochondria Pathway, etc
Molecular Cloning(DNA, RNA, PCR)
Vector, Carrier, Formulation
(Aedes aegypti model)
Bioassays
Molecular Pesticide Construction
Control Molecular Pesticide 1
Molecular Pesticide 2 Molecular Pesticide 3
Cell Assay
Evaluation of Molecular Pesticides
Adult Assay
Evaluation of Molecular Pesticides
Control Molecular Pesticides
1)Cell and adult assays have demonstrated that critical pathways can be targeted to develop molecular pesticides
2)Using Aedes aegypti as a model organism, molecular pesticides are effective and fast-killing (within 6 hours)
SummaryDevelopment of Molecular Pesticides
1)Identify new critical pathways to target
2)Produce additional molecular pesticides and evaluate their efficacy
3)Select best molecular pesticides and evaluate production and application methods (formulation, carriers, etc)
Future StudiesDevelopment of Molecular Pesticides
Overall Summary
1)Screened known registered pesticides; several showed high insecticidal activity
2)Screened different natural plant chemicals (NPURU), two had relatively high toxicities against mosquitoes
Overall Summary (Cont’d)
3) Screened 33 piperidines (UF & NPURU) with different structures, 2-ethyl piperidine showed the highest toxicity (in press in JME)
4) Cell and adult assays have demonstrated that critical pathways can be targeted to develop molecular pesticides (patent pending)
5) Using Aedes aegypti as a model organism, molecular pesticides are effective and fast-killing (within 6 hours)
AcknowledgmentsDr. James J. BecnelDr. Gary G. ClarkDr. Sandra AllanDr. Dan KlineDr. Ulrich Bernier
Dr. Brian QuinnDr. Chris GedenDr. Roberto PereiraDr. Jerry HogsetteDr. Ken Linthicum
Dr. Liming ZhaoHeather FurlongGreg AllenNathan NewlonJoyce Urban
Mosquito and Fly Research Unit, USDA-ARS-CMAVE
Dr. Kumudini Meepagala
Natural Products Utilization Research Unit, USDA-ARS
Dr. Alan Katritzky Department of Chemistry, University of Florida
Dr. Daniel Strickman
National Program Leader, Program 104, USDA-ARS
Dr. Graham WhiteDepartment of Entomology, University of Florida
Deployed War-Fighter Protection Research Program