Insect-specific irreversible inhibitors of acetylcholinesterase in pests including the bed bug, the eastern yellowjacket, German and American cockroaches, and the confused flour beetle

Polsinelli, Gregory A.; Singh, Sanjay; Mishra, Rajesh; Suranyi, Robert A.; Ragsdale, David W.; Pang, Yuan Ping; Brimijoin, Stephen

doi:10.1016/j.cbi.2010.01.036

Cited by 18 publications

(13 citation statements)

References 31 publications

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“…The failure of this reagent to achieve higher recovery of enzyme activity (through deconjugation of the covalently bound inhibitor from C286) was attributed to the observed high sensitivity of apo- Ag AChE to this reagent. Progressive inhibition of the AChEs present in beetle and cockroach homogenate was also demonstrated with 3l , by following the decrease in enzyme velocity with increasing incubation time at 6 μM over 70 min [34]. To assess the level of reactivity needed to ligate Cys286, the less reactive 1° bromide 4 was then assessed as an inhibitor.…”

Section: Development Of Covalent Inhibitors Of An Gambiae Ache Thmentioning

confidence: 99%

Discovery of Species-selective and Resistance-breaking Anticholinesterase Insecticides for the Malaria Mosquito

Carlier

Bloomquist

Totrov

et al. 2017

CMC

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Great reductions in malaria mortality have been accomplished in the last 15 years, in part due to the widespread roll-out of insecticide-treated bednets across sub-Saharan Africa. To date, these nets only employ pyrethroids, insecticides that target the voltage-gated sodium ion channel of the malaria vector, Anopheles gambiae. Due to the growing emergence of An. gambiae strains that are resistant to pyrethroids, there is an urgent need to develop new public health insecticides that engage a different target and possess low mammalian toxicity. In this review, we will describe efforts to develop highly species-specific and resistance-breaking inhibitors of An. gambiae acetylcholinesterase (AgAChE). These efforts have been greatly aided by advances in knowledge of the structure of the enzyme, and two major inhibitor design strategies have been explored. Since AgAChE possesses an unpaired Cys residue not present in mammalian AChE, a logical strategy to achieve selective inhibition involves design of compounds that could ligate that Cys. A second strategy involves the design of new molecules to target the catalytic serine of the enzyme. Here the challenge is not only to achieve high inhibition selectivity vs human AChE, but also to demonstrate toxicity to An. gambiae that carry the G119S resistance mutation of AgAChE. The advances made and challenges remaining will be presented. This review is part of the special issue “Insecticide Mode of Action: From Insect to Mammalian Toxicity.

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Section: Development Of Covalent Inhibitors Of An Gambiae Ache Thmentioning

confidence: 99%

Discovery of Species-selective and Resistance-breaking Anticholinesterase Insecticides for the Malaria Mosquito

Carlier

Bloomquist

Totrov

et al. 2017

CMC

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“…Recent sequence analyses [48, 65] expanded the list to 22 insects with AP-AChEs that have a cysteine residue equivalent to Cys289 of the greenbug AP-AChE by adding the yellow fever mosquito, the cat flea, the wild silkmoth, the red flour beetle, the jewel wasp, and the sand fly. Although the AP-AChE sequences have not yet been reported, a recent biochemical study [66] provides direct evidence that yellow jacket wasp ( Vespula maculifrons ), Asian ladybird beetle ( Harmonia axyridis ), the American cockroach ( Periplaneta americana ), and the bed bug ( Cimex lectularius ) also have AP-AChE equivalent to that in the greenbug. …”

Section: Insect-specific Cysteine In Acetylcholinesterasesmentioning

confidence: 99%

Novel and Viable Acetylcholinesterase Target Site for Developing Effective and Environmentally Safe Insecticides

Pang¹,

Brimijoin²,

Ragsdale³

et al. 2012

CDT

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Insect pests are responsible for human suffering and financial losses worldwide. New and environmentally safe insecticides are urgently needed to cope with these serious problems. Resistance to current insecticides has resulted in a resurgence of insect pests, and growing concerns about insecticide toxicity to humans discourage the use of insecticides for pest control. The small market for insecticides has hampered insecticide development; however, advances in genomics and structural genomics offer new opportunities to develop insecticides that are less dependent on the insecticide market. This review summarizes the literature data that support the hypothesis that an insect-specific cysteine residue located at the opening of the acetylcholinesterase active site is a promising target site for developing new insecticides with reduced off-target toxicity and low propensity for insect resistance. These data are used to discuss the differences between targeting the insect-specific cysteine residue and targeting the ubiquitous catalytic serine residue of acetylcholinesterase from the perspective of reducing off-target toxicity and insect resistance. Also discussed is the prospect of developing cysteine-targeting anticholinesterases as effective and environmentally safe insecticides for control of disease vectors, crop damage, and residential insect pests within the financial confines of the present insecticide market.

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“…The BgAChE1 (ace1) proteins usually represent 65-75% of the total active AChE in the B. germanica nerve tissue, which is the main target of organophosphate insecticides in cockroaches. Considering the use of praguicides in agriculture and in insect control may represent a potential danger, the search for new insecticides that might act on a specific residue of the insect AChE, be free of resistance and be less toxic for mammals, birds and fish is still in progress (Badea et al, 2006, Polsinelli et al, 2010. The effects of antx-a(s) in the environment should be further investigated, as there are few reports about its biological activity in different species, such as insects.…”

Section: Effects Of a Cyanobacterial Extract Containing Anatoxin-a(s)mentioning

confidence: 99%

Effects of a cyanobacterial extract containing-anatoxin-a(s) on the cardiac rhythm of Leurolestes circunvagans

Rodríguez

Mori

Belo³

et al. 2012

Rev. bras. farmacogn.

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This work presents the effects of an anatoxin-a(s) containing extract on a cockroach semi-isolated heart preparation and the results supporting the extract's biological activity on acetylcholinesterase (purifi ed from eel). The presence of the toxin in cyanobacterial strains Anabaena spiroides (ITEP-024, ITEP-025 and ITEP-026) isolated from the Tapacurá reservoir in Pernambuco, Brazil, was confi rmed by means of liquid chromatography coupled to an ion-trap mass spectrometer. The anticholinesterase activity was assessed biochemically by the Ellman test and was confi rmed by measuring the cockroach's heart rate. The concentration of the extract containing the tested anatoxina(s) (antx-a(s)) (10, 16 and 100 μg.μL -1 ) inhibited the eel acetylcholinesterase (AChE) by more than 90%. The cockroach cardiac frequency increased by a maximum of about 20% within 29 min after the addition of 2.5x10 3 μg of extract containing antx-a(s).g -1 bw (n=9, p<0.05). Our results strongly indicate that antx-a(s) is capable of exerting biological effects on cockroach, indicating that more research might be conducted to determine its role in the environment, especially on insects.

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Insect-specific irreversible inhibitors of acetylcholinesterase in pests including the bed bug, the eastern yellowjacket, German and American cockroaches, and the confused flour beetle

Cited by 18 publications

References 31 publications

Discovery of Species-selective and Resistance-breaking Anticholinesterase Insecticides for the Malaria Mosquito

Discovery of Species-selective and Resistance-breaking Anticholinesterase Insecticides for the Malaria Mosquito

Novel and Viable Acetylcholinesterase Target Site for Developing Effective and Environmentally Safe Insecticides

Effects of a cyanobacterial extract containing-anatoxin-a(s) on the cardiac rhythm of Leurolestes circunvagans

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