Chitin, synthesis

Since diflubenzuron toxicity seems to be similar in both insects and crustaceans, extreme care must be taken when this compound and other chitin synthesis inhibitors are used for insect control in areas where aquatic crustaceans occur. Otherwise, ecological instability may result, with consequences... 

El-Gazzar, L.M., R.S. Patterson, and P.G. Koehler. 1988. Activity of chitin synthesis inhibitors on the cat flea, Ctenocephalides felis Bouche. Jour. Agricul. Entomol. 5 117-120. 

Ho, C.M., T.R. Hsu, J.Y. Wu, and C.H. Wang. 1987. Effect of dimilin, a chitin synthesis inhibitor, on the growth and development of larvae of Aedes albopictus Skuse. Chinese Jour. Entomol. 7 131-141. 

Marx, J.L. 1977. Chitin synthesis inhibitors new class of insecticides. Science 197 1170-1172. 

Muzzarelli, R. 1986. Chitin synthesis inhibitors effects on insects and on nontarget organisms. CRC Crit. Rev. Environ. Control 16 141-146. 

Both compounds included here are experimental and in each case the pyridine is a benzene replacement and is not essential for the activity. The urea (103) (79SAP7802440) is a member of a highly active series that kill insects by disrupting the formation of new insect cuticle, through inhibition of chitin synthesis. The cyclopropane ester (104) (78GEP2810881) is a heterocyclic analogue of the pyrethroid insecticides, an extremely successful new class which are active on a wide range of insects. 

Chitin Synthesis Inhibitors. These are insect growth regulators that prevent the formation of the insect chitinous exoskeleton and thus produce a critical biochemical lesion during hatching, ecdysis, or pupation (44). These complex biochemical and physiological processes are unique to arthropods therefore, the benzoyl phenyl ureas are highly specific insecticides (44). 

Insects exposed to diflubenzuron and related compounds are unable to form normal cuticle (skin) because their ability to synthesize it is lost. Thus, the cuticle becomes thin and brittle, and is unable to support the insect or to withstand molting, a process requiring the shedding of the old cuticle, as in metamorphosis. Diflubenzuron and other chitin synthesis inhibitors have extremely low mammalian toxicity and are used against termites. 

I. Hammann, W. Sirrenberg, Laboratory evaluation of SIR 8514, a new chitin synthesis inhibitor of the benzoylated urea class, Pflanzenschutz-Nachr. 33 (1) (1980) 1-34. 

We urge research on screening procedures so that they may be more directly aimed at the fungal life processes (chitin synthesis, for example) that are different from host or human rocesses. 

Recently, Nishimura et at. (47) have reported the discovery of polyoxin resistant strains of A. kikuehiana in some orchards of Tottori Prefecture, Japan. Hori et at. (48) suggested that the resistance is caused by a lowered permeability of the antibiotic through the cell membrane into the site of chitin synthesis. 

Figure 8. Rate of inhibition of chitin synthesis after injection of diflu-benzuron in fifth instar Pieris brassicae larvae 24 hr after ecdysis...

Figure 10. Biosynthetic pathway of chitin synthesis from glucose...

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 addition to the effects of diflubenzuron on the chitinase and phenoloxidase levels, observed by Ishaaya and Casida (4 6), other biochemical influences of diflubenzuron and Du 19111 have been described in the literature (Table 9) A common feature of all these effects is their analysis one or more days after treatment. As any effects of these benzoyl-phenyl ureas become visible on the living insects only at the time of the next moult, when susceptible larvae die, investigators are prompted to search for defects up to a considerable time after application. In comparison with the very fast inhibition of chitin synthesis discussed above, in our opinion these studies can at the most indicate "secondary" effects. A considerable number of effects of this type can be expected to be found and published in the future. 

Summarizing, diflubenzuron features mentioned in the introduction of this paper can be completed as follows The new insecticide has favourable environmental properties because it is non-persistent in soils and it has a low biological magnification. It is stable on plants and in insects, hence it has a long residual activity. It represents the best choice from the series of the benzoylphenyl ureas. It is a reversible inhibitor of chitin synthesis in insects, probably by blocking chitin synthetase. 

Chitin synthesis inhibitor and so interferes with the formation of insect cuticle... 

Buprofezin / A, / S (Cyclic urea) ) N NC(CH,j)3 N 0 CH(CHj)2 Probable chitin synthesis and prostaglandin inhibitor. Hormone disturbing effect, leading to suppression of ecdysis... 

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