Inhibition of chitin synthesis

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. 

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

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. 

Gijswijt, M.J., Deul, D.H., and de Jone, B.J., Inhibition of chitin synthesis by benzoyl-phenylurea insecticides. III. Similarity in action in Pieris brassicae (L.) with Polyoxin D, Pestic. Biochem. Physiol., 12, 87,1979. 

Hector RE, Pappagianis D. Inhibition of chitin synthesis in the cell wall of Coccidioides immitis by polyoxin D. 

Metalaxyl is a member of a class of compounds that structurally resemble the chloroacetani-lides however, it is a systemic fungicide. Diflubenzuron is representative of a class of insecticides that owe their action to inhibition of chitin synthesis by the developing insect. Metalaxel and diflubenzuron are good examples of compounds prepared by the synthesis chemist as herbicide candidates that have commercial levels of activity in entirely different applications. Such examples point out the need for a balanced synthesis and screening program for the development of new agrochemicals. 

Diflubenzuron inhibits the enzyme chitin synthase, which is required in the final step of chitin synthesis. Chitin is a polysaccharide and a major constituent of the exoskeleton of insects. In insects, the trachea is held open by rings of chitin. The exoskeleton and waxy covering also prevent water loss. Inhibiting chitin synthesis therefore can provide an effective means of pest control. Moreover, vertebrates and most plants do not utilize chitin, thus making diflubenzuron a target-selective pesticide. 

PaUi SR, Retnakaran A. Molecular and biochemical aspects of chitin synthesis inhibition. EXS 1999, 87, 85-98. 

Chitin synthesis in fungi is commonly very rapidly sensitive to the inhibition of protein synthesis by agents such as cycloheximide (Ryder and Peberdy, 1979 Farkas and Svoboda, 1980). The reason for this appears to be related to the need for a continuing production of chitin synthetase, rather than a requirement for a glycoprotein primer, as Ryder and Peberdy (1979) have... 

Abo-Elghar, G. E., Fujiyoshi, P., and Matsumura, F., Significance of the sulfonylurea receptor (SUR) as the target of diflubenzuron in chitin synthesis inhibition in Drosophila melanogaster and Blat-tella gertnanica, Insect Biochem. Molec. Biol., 34, 743, 2004. 

Some pesticides, such as the herbicides inhibiting synthesis of amino acids in plants, are extremely selective between plants and animals and very potent. The chitin synthesis inhibitors used as insecticides are also extremely selective, because only insects and crustaceans (and fungi) make chitin. The fungicides first described are also efficient and have a high degree of selectivity, but are likely to produce effects in animals and plants because they inhibit enzymes of great importance to many types of organisms. 

Buprofezin is a specific poison for Homoptera, but the mode of action is not known. It is included in this chapter because it probably interferes with molting or chitin synthesis in some way It inhibits embryogenesis and progeny formation of some insects at very low concentrations (see Ishaaya, 1992). Cyromazil was first marketed in 1980 and is an insect growth regulator. Insect larvae, particularly fly larvae, develop cuticular lesions before they eventually die. 

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