TY - JOUR
T1 - Insect-specific irreversible inhibitors of acetylcholinesterase in pests including the bed bug, the eastern yellowjacket, German and American cockroaches, and the confused flour beetle
AU - Polsinelli, Gregory A.
AU - Singh, Sanjay K.
AU - Mishra, Rajesh K.
AU - Suranyi, Robert
AU - Ragsdale, David W.
AU - Pang, Yuan Ping
AU - Brimijoin, Stephen
N1 - Funding Information:
This work was supported by the Minnesota Partnership for Medical Genomics and Biotechnology , the U.S. Army Medical Research & Materiel Command (W81XWH-08-1-0154), the Mayo Foundation for Medical Education and Research , the University of Minnesota/Mayo/IBM Collaboration Seed Grant Program , and the University of Minnesota Supercomputing Institute .
PY - 2010/9
Y1 - 2010/9
N2 - Insecticides directed against acetylcholinesterase (AChE) are facing increased resistance among target species as well as increasing concerns for human toxicity. The result has been a resurgence of disease vectors, insects destructive to agriculture, and residential pests. We previously reported a free cysteine (Cys) residue at the entrance to the AChE active site in some insects but not higher vertebrates. We also reported Cys-targeting methanethiosulfonate molecules (AMTSn), which, under conditions that spared human AChE, caused total irreversible inhibition of aphid AChE, 95% inhibition of AChE from the malaria vector mosquito (Anopheles gambia), and >80% inhibition of activity from the yellow fever mosquito (Aedes aegypti) and northern house mosquito (Culex pipiens). We now find the same compounds inhibit AChE from cockroaches (Blattella germanica and Periplaneta americana), the flour beetle (Tribolium confusum), the multi-colored Asian ladybird beetle (Harmonia axyridis), the bed bug (Cimex lectularius), and a wasp (Vespula maculifrons), with IC50 values of ∼1-11μM. Our results support further study of Cys-targeting inhibitors as conceptually novel insecticides that may be free of resistance in a range of insect pests and disease vectors and, compared with current compounds, should demonstrate much lower toxicity to mammals, birds, and fish.
AB - Insecticides directed against acetylcholinesterase (AChE) are facing increased resistance among target species as well as increasing concerns for human toxicity. The result has been a resurgence of disease vectors, insects destructive to agriculture, and residential pests. We previously reported a free cysteine (Cys) residue at the entrance to the AChE active site in some insects but not higher vertebrates. We also reported Cys-targeting methanethiosulfonate molecules (AMTSn), which, under conditions that spared human AChE, caused total irreversible inhibition of aphid AChE, 95% inhibition of AChE from the malaria vector mosquito (Anopheles gambia), and >80% inhibition of activity from the yellow fever mosquito (Aedes aegypti) and northern house mosquito (Culex pipiens). We now find the same compounds inhibit AChE from cockroaches (Blattella germanica and Periplaneta americana), the flour beetle (Tribolium confusum), the multi-colored Asian ladybird beetle (Harmonia axyridis), the bed bug (Cimex lectularius), and a wasp (Vespula maculifrons), with IC50 values of ∼1-11μM. Our results support further study of Cys-targeting inhibitors as conceptually novel insecticides that may be free of resistance in a range of insect pests and disease vectors and, compared with current compounds, should demonstrate much lower toxicity to mammals, birds, and fish.
KW - Acetylcholinesterase
KW - Agricultural pest
KW - Disease vector
KW - Inhibitor
KW - Insecticide resistance
KW - Methanethiosulfonate
KW - Residential pest
KW - Sulfhydryl group
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U2 - 10.1016/j.cbi.2010.01.036
DO - 10.1016/j.cbi.2010.01.036
M3 - Article
C2 - 20109441
AN - SCOPUS:77955509182
SN - 0009-2797
VL - 187
SP - 142
EP - 147
JO - Chemico-biological interactions
JF - Chemico-biological interactions
IS - 1-3
ER -