Transcript Slide 1

DWFP Toxicology Research to
Develop Insecticides for Vector Control
Julia W. Pridgeon, PhD
Toxicologist/Molecular Biologist
02-14-07
Mosquito and Fly Research Unit
Center for Medical, Agricultural, and
Veterinary Entomology
USDA-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 Plant
Chemicals
IRAC
USDA-ARSNPURU
Plant Extracts
USDA-ARSMFRU
Designer
Chemicals
NPURU & UF
High-Throughput Screen to find highly toxic chemical
(Topical application; Aedes aegypti model)
Small Chamber Test and Field Evaluation
Topical Application
Small Amount
Accurate
Fast
Easy
Results of Studies on Chemical Insecticides
26
19
Registered
Pesticides
Natural Plant
Chemicals
USDA-ARSNPURU
IRAC
Pesticide
LD50 (ug)
Fipronil
1.3 10-6
Permethrin
1.4 10-4
Spinosad
2.5 10-3
Bifenzate
4.25
AT-05-27-2
(LD50 0.3ug)
123-1
(LD50 = 0.4ug)
33
Plant Extracts
USDA-ARSMFRU
Bacopa monnieri
(Water hyssop)
Methanol Extract
LD50 125ug
33
Designer
Chemicals
NPURU & UF
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
Summary on Studies of
Chemical Insecticides
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)
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
Future Studies on Chemical Pesticides
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
Approach for the Development
of Molecular Pesticides
Target Essential
Pathways
Programmed Cell Death,
Mitochondria Pathway, etc
Molecular Cloning
(DNA, RNA, PCR)
(Aedes aegypti model)
Vector, Carrier, Formulation
(Aedes aegypti model)
Bioassays
Molecular Pesticide
Construction
Evaluation of Molecular Pesticides
Cell Assay
Control
Molecular Pesticide 2
Molecular Pesticide 1
Molecular Pesticide 3
Evaluation of Molecular Pesticides
Adult Assay
Control
Molecular Pesticides
Summary
Development of 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 fastkilling (within 6 hours)
Future Studies
Development 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)
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 fastkilling (within 6 hours)
Acknowledgments
Dr. James J. Becnel
Dr. Gary G. Clark
Dr. Sandra Allan
Dr. Dan Kline
Dr. Ulrich Bernier
Dr. Brian Quinn
Dr. Chris Geden
Dr. Roberto Pereira
Dr. Jerry Hogsette
Dr. Ken Linthicum
Dr. Liming Zhao
Heather Furlong
Greg Allen
Nathan Newlon
Joyce Urban
Mosquito and Fly Research Unit, USDA-ARS-CMAVE
Dr. Kumudini Meepagala
Natural Products Utilization Research Unit, USDA-ARS
Dr. Daniel Strickman
National Program Leader, Program 104, USDA-ARS
Dr. Alan Katritzky
Department of Chemistry, University of Florida
Dr. Graham White
Department of Entomology, University of Florida
Deployed War-Fighter Protection Research Program