Mechanism of inhibition reaction of acetylcholinesterase by phenyl N-methylcarbamates

Nishi­oka, Takaaki; Fujita, Toshio; Kamoshita, Katsuzo; Nakajima, Minoru

doi:10.1016/0048-3575(77)90023-2

Cited by 31 publications

(29 citation statements)

References 22 publications

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“…Owing to the intrinsic reactivity of methylcarbamate esters, an electron-withdrawing substituent is not required in the aryl moiety for high anticholinesterase activity. In fact, the introduction of a nitro substituent into the phenyl ring of phenyl methylcarbamate results in a compound of such high reactivity that it is hydrolytically degraded before it has an opportunity to inhibit the enzyme (22). It Methylcarbamates of substituted phenols and oximes with good complementary fit to the enzyme active site are generally strong inhibitors of AChE (21).…”

Section: Reactivity and Steric Propertiesmentioning

confidence: 99%

Mechanism of Action of Organophosphorus and Carbamate Insecticides

Fukuto¹

1990

Environmental Health Perspectives

205

255

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Organophosphorus and carbamate insecticides are toxic to insects and mammals by virtue of their ability to inactivate the enzyme acetylcholinesterase. This review addresses the mechanism of inhibition of acetylcholinesterase by organophosphorus and carbamate esters, focusing on structural requirements necessary for anticholinesterase activity. The inhibition of acetylcholinesterase by these compounds is discussed in terms of reactivity and steric effects. The role of metabolic activation or degradation in the overall intoxication process is also discussed.

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Section: Reactivity and Steric Propertiesmentioning

confidence: 99%

Mechanism of Action of Organophosphorus and Carbamate Insecticides

Fukuto¹

1990

Environmental Health Perspectives

205

255

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“…While on-target (M. domestica AChE) and insect in vivo structureeactivity relationships for insecticidal CBs are available for a large number of derivatives (Metcalf, 1971), only a small number of direct comparisons of CB AChE target selectivities, using enzymes from insect pest species and from vertebrates, have been published (Nishioka et al, 1977;Kamoshita et al, 1979;Carlier et al, 2008). In this study, 23 CB insecticides, most of them commercial products, were investigated for on-target selectivities.…”

Section: Discussionmentioning

confidence: 99%

The characterization of Lucilia cuprina acetylcholinesterase as a drug target, and the identification of novel inhibitors by high throughput screening

Ilg¹,

Cramer²,

Lutz³

et al. 2011

Insect Biochemistry and Molecular Biology

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“…It is similar to the MR term in equations 19 and 20. However, it is different from the Eg term in equation 25. A point which must be kept in mind is that the variation in the size of the substituents in most of the studies is not large.…”

Section: Insect Cholinesterasementioning

confidence: 95%

“…Inhibition of human plasma enzyme by COOC2H5 (22) log 1/Ki = 0.38 π + 3.58 η = 10, r 2 = 0.980, s = 0.059 (22) Inhibition of human plasma enzyme by Ο / \ oH 2 rN^^-C^ C lft H,,-N" >-ONHR (25) log 1/C = 0.74 π + 4.12 n = 9, r 2 = 0.970, s = 0.103…”

Section: Insect Cholinesterasementioning

confidence: 99%

“…Inhibition of electric eel enzyme by Inhibition of bovine erythrocyte enzyme by Ο X-C 6 H 4 OCNHCH 3 (25) log 1/K = 1.40 π-23 + 0.30 π 4 + 1.66 σ° -1.78 σ 2 + 0.17 Eg + 0.77 F-2 + 1.36 HB + 0.07 η = 53, r 2 = 0.897, s = 0.238 (25) The above QSAR was first published using MR (molar refractivity) instead of π (25). We have found that π yields a better correlation.…”

Section: Insect Cholinesterasementioning

confidence: 99%

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Comparative Quantitative Structure—Activity Relationship

Hansch¹

1995

ACS Symposium Series

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To construct a science of quantitative structure-activity relationships (QSAR) we must begin to do comparative studies of QSAR in many different systems. In this way we can begin to understand the similarities in different compounds interacting with the same biological system and different biological systems interacting with the same compounds. Examples are given for the inhibition of insect and vertebrate cholinesterase by a variety of chemicals. For the inhibition of vertebrate enzyme the hydrophobic properties of the inhibitors is important, but not for fly enzyme.Since the initiation of the QSAR paradigm in 1962 (7) thousands of quantitative structure-activity relationships have been published for all kinds of organic compounds acting on all sorts of organisms or parts thereof (DNA, enzymes, organelles, etc.). In addition to these, physical organic chemists have been hard at work since 1935 formulating quantitative relationships for organic reactions in solution. Our own data bank, which is only a fraction of the literature, contains about 6,000 examples about equally divided between biological and organic chemistry. The time has come to begin the serious organization and generalization of this mass of published and still rapidly growing work Already it is possible to make interesting comparisons and generalizations (2-5). We believe that it is particularly important to tie the less certain biological QSAR to the more firmly based relationships established by physical organic chemists (2, J). Before considering the central topic of this report, it helps to illustrate our general approach with a few diverse examples.Many years ago (3) we derived equation 1 for the colchicine-like mitosis in onion root tips caused by simple organic solvents such as: alcohols, acetone, CHCI3, xylene, ether, etc.log 1/C = 0.95 log Ρ + 0.63 η = 22, r* = 0.916, s = 0.381 (1)In this equation, C is the molar concentration of chemical producing the standard aberrant mitosis. This seemed a highly esoteric study only of academic interest, still we entered it into our bank. Recently, we came across equation 2 by Onfelt

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Mechanism of inhibition reaction of acetylcholinesterase by phenyl N-methylcarbamates

Cited by 31 publications

References 22 publications

Mechanism of Action of Organophosphorus and Carbamate Insecticides

Mechanism of Action of Organophosphorus and Carbamate Insecticides

The characterization of Lucilia cuprina acetylcholinesterase as a drug target, and the identification of novel inhibitors by high throughput screening

Comparative Quantitative Structure—Activity Relationship

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