Abstract
Methamidophos (Met) is a weak inhibitor of housefly head AChE but at the same time it is highly toxic to the common housefly. The lethality of Met is believed to be due to AChE inhibition. An extensive QSAR study may help in determining the mode of action of Met in vivo and in vitro and provide a rational for its high insecticidal toxicity. Acephate (Ace), like Met, is a poor inhibitor of AChE in vitro and has a comparable to Met insect toxicity in vivo. Contrary to Met, though, Ace has much lower mammalian toxicity. Understanding the structural properties which make insecticides toxic to insects but not to mammals is of great importance, since mammals (including humans) are inadvertently exposed to these compounds. Our results were consistent with the model in which both the in vitro and in vivo toxicity of Met depends on the inhibition of the active center of AChE by the unchanged Met. An optimal susceptibility to hydrolysis is needed for Met and its analogs to have high insecticidal activity since in order to phosphorylate AChE they need to be hydrolyzed and at the same time their stability is of great importance in vivo for accumulating at the site of action. The insecticidal activity of Ace analogs may be due to direct interaction with the active center of the AChE. The mammalian toxicity of Ace analogs may be due to interaction with an 'allosteric' reaction center in the AChE.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 453-471 |
| Number of pages | 19 |
| Journal | SAR and QSAR in Environmental Research |
| Volume | 11 |
| Issue number | 5-6 |
| DOIs | |
| State | Published - Jan 1 2001 |
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QSAR for acetylcholinesterase inhibition and toxicity of two classes of phosphoramidothioates. / Spassova, D. P.; Singh, Ashok K.
In: SAR and QSAR in Environmental Research, Vol. 11, No. 5-6, 01.01.2001, p. 453-471.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - QSAR for acetylcholinesterase inhibition and toxicity of two classes of phosphoramidothioates.
AU - Spassova, D. P.
AU - Singh, Ashok K
PY - 2001/1/1
Y1 - 2001/1/1
N2 - Methamidophos (Met) is a weak inhibitor of housefly head AChE but at the same time it is highly toxic to the common housefly. The lethality of Met is believed to be due to AChE inhibition. An extensive QSAR study may help in determining the mode of action of Met in vivo and in vitro and provide a rational for its high insecticidal toxicity. Acephate (Ace), like Met, is a poor inhibitor of AChE in vitro and has a comparable to Met insect toxicity in vivo. Contrary to Met, though, Ace has much lower mammalian toxicity. Understanding the structural properties which make insecticides toxic to insects but not to mammals is of great importance, since mammals (including humans) are inadvertently exposed to these compounds. Our results were consistent with the model in which both the in vitro and in vivo toxicity of Met depends on the inhibition of the active center of AChE by the unchanged Met. An optimal susceptibility to hydrolysis is needed for Met and its analogs to have high insecticidal activity since in order to phosphorylate AChE they need to be hydrolyzed and at the same time their stability is of great importance in vivo for accumulating at the site of action. The insecticidal activity of Ace analogs may be due to direct interaction with the active center of the AChE. The mammalian toxicity of Ace analogs may be due to interaction with an 'allosteric' reaction center in the AChE.
AB - Methamidophos (Met) is a weak inhibitor of housefly head AChE but at the same time it is highly toxic to the common housefly. The lethality of Met is believed to be due to AChE inhibition. An extensive QSAR study may help in determining the mode of action of Met in vivo and in vitro and provide a rational for its high insecticidal toxicity. Acephate (Ace), like Met, is a poor inhibitor of AChE in vitro and has a comparable to Met insect toxicity in vivo. Contrary to Met, though, Ace has much lower mammalian toxicity. Understanding the structural properties which make insecticides toxic to insects but not to mammals is of great importance, since mammals (including humans) are inadvertently exposed to these compounds. Our results were consistent with the model in which both the in vitro and in vivo toxicity of Met depends on the inhibition of the active center of AChE by the unchanged Met. An optimal susceptibility to hydrolysis is needed for Met and its analogs to have high insecticidal activity since in order to phosphorylate AChE they need to be hydrolyzed and at the same time their stability is of great importance in vivo for accumulating at the site of action. The insecticidal activity of Ace analogs may be due to direct interaction with the active center of the AChE. The mammalian toxicity of Ace analogs may be due to interaction with an 'allosteric' reaction center in the AChE.
UR - http://www.scopus.com/inward/record.url?scp=0035261018&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035261018&partnerID=8YFLogxK
U2 - 10.1080/10629360108035363
DO - 10.1080/10629360108035363
M3 - Article
VL - 11
SP - 453
EP - 471
JO - SAR and QSAR in Environmental Research
JF - SAR and QSAR in Environmental Research
SN - 1062-936X
IS - 5-6
ER -