Intrinsic Insecticidal Activity

The relative lethal efficacy of metofluthrin to d-allethrin by topical application for 4 medically important mosquito species is given in Table I. The lethal efficacy of metofluthrin is 19 to 49 times as high as d-allethrin and also superior to that of permethrin. 

Metofluthrin in particular has an extremely high lethal efficacy against mosquitoes. 

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Insecticidal activities of plant metabohtes can be demonstrated by their effect on insects when added to artificial diets (De Boer and Hanson, 1987 Broadway and Duffey, 1988 Snook et al, 1997 Jassbi et al, 2006). However, comparative quantification between the toxicity of metabolites applied artificially and amounts measured in whole plant extracts are potentially misleading because of the lower intrinsic acceptability of artificial diets. Compounds within plants may have additional effects that deter insects indirectly, and these defence mechanisms are discussed later in this chapter (see Section Higher Trophic Level Interactions ). 

It Is well known that phosphorothlonate insecticides such as parathlon (, 0-diethyl p-nitrophenyl phosphorothloate) and malathion [0, -dimethyl -(l,2 -dlcarbethoxy)ethyl phosphoro-dithioate] are Intrinsically poor inhibitors of acetylcholinesterase and in vivo activation to the respective anticholinesterases paraoxon and malaoxon is required before animals exposed to the phosphorothionates are intoxicated. Since metabolic activation is essential to the biological activity of these thiono sulfur-containing organophosphorus insecticides, compounds of this type may be considered as propesticides or, more specifically, prolnsectlcldes. 

In this context the comparison of the insecticide diflubenzuron with the fungicide polyoxin D is interesting in more than one respect. It not only closes the circle in our paper, so to speak, but it can also furnish strong circumstantial evidence to support our hypothesis of the mode of action of diflubenzuron. Marks and Sowa were the first to compare diflubenzuron and polyoxin D in their effects on the A ecdyson-dependent in-vitro synthesis of chitin by the cockroach (Leucophaea maderae) leg regenerates (4, ) These authors found that both compounds almost completely inhibited the incorporation of C-labeled D-glucosamine into the chitin fraction. In a later study with 1 C-labeled N-acetyl-D-glucosamine similar results were obtained, and the I50 value of inhibition of chitin synthesis was found to be 6.1 1 x 10 -10m for diflubenzuron and 7.53 x 10"7 M for polyoxin D (4 8) The difference in intrinsic activity can partly be explained by the roughly hundredfold accumulation of dif lubenzuron in the insect tissue. 

In this equation, tt is the hydrophobic parameter, sc the Hancock steric parameter, and a the electronic constant for the bridgehead substituent. Median lethal dose is expressed as mol/fly. The bicy-clic phosphates have been shown to be mainly degraded by microsomal mixed-function oxidases in the housefly (12). Thus, the toxicity determined by injection after pb pretreatment is regarded as a good measure of the intrinsic toxicity of BPs, and it is probable that this equation reflects significant interactions between the bridgehead substituent of BPs and its site of action, i.e., a type of receptor. Little is known about the hypothetical BP receptor in the insect while a considerable amount of information has been obtained on a mammalian site. Three-dimensional receptor models have been proposed based on structure-activity relationships for BPs and related compounds (13,14). It is now important to substantiate the existence of the putative receptor in insects for the elucidation of the detailed mode of insecticidal action of BPEs. 

Five amides, 50(n=4,6), 55, 5 and 6(n=6), isolated from P. guineense were investigated by Candy and co-workers [10] with respect to their knockdown and lethal activity against adult houseflies, as well as the rates of recovery of M. domestica from the effects of sublethal doses of the amides. As with other insecticides, rapid and potent knockdown activity on topical application of the amides depends, apart from the intrinsic toxicities of the individual compounds, on their ability to penetrate the cuticle and relevant membranes en route to the site of action. Attempts to correlate knockdown activity in the P. guineense amide series with polarity on this basis seemed to show some inconsistencies, perhaps as a result of steric factors [10,102]. The rate of recovery from the effects of sub-lethal doses of insecticides is associated, inter alia, with processes that lead to removal of the toxicant, so that recovery from treatment with Piper amides embodying the methylenedioxyphenyl group, which retards the action of mixed function oxidases, is slower than recovery from the effects of the less stable aliphatic amides. 

Clark realized this, and said The action of acetylcholine depends on at least two separable factors, firstly the fixation of the drug by certain receptors, and secondly the power to produce its action after fixation (Clark, 1937). Further experimental work in Holland established these concepts firmly under the names affinity and intrinsic activity respectively (Ariens, 1954). An inhibitor (e.g. a chemotherapeutic drug, insecticide, or fungicide) requires only affinity but many pharmacodynamic drugs must have intrinsic activity as well, namely the... 

Several studies have shown that chemical compounds containing specific functional groups or features are more effective arthropod repellents as measured by the duration of protection. - Recently, we reported a study of similar analysis of stereoelectronic properties (steric and intrinsic electronic properties) between natural insect JH, a synthetic insecticide (JH-mimic, undecen-2-yl carbamate), and deet and its analogs. Structure-activity studies on JHs have resulted in the discovery of JH-like compounds that mimic the morphogenetic activity of JH with the aim of controlling insect populations. 

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