Ecdysis inhibitors

Another limonoid isolated from neem seeds and determined to be as potent as azadirachtin as an ecdysis inhibitor has been identified as 3-deacetylazadirachtinol (Figure 15) (57). Both compounds were lethal to 50% of the treated H. virescens larvae (EI5Q) at 0.8 ppm in artificial diet (Table VII). Structurally, there are two differences between the compounds. In 3-deacetylazadirachtinol, the C-ll-O-C-13 ether linkage of azadirachtin is reductively cleaved at the 11 position and the acetoxyl group at C-3 is hydrolyzed to a hydroxyl group. 

Figure 15. 3-Deacetylazadirachtinol, a Potent Insect Ecdysis Inhibitor Isolated from the Seeds of Azadirachta indica (57)...

Isolation of Phytoecdysones as Insect Ecdysis Inhibitors and Feeding Deterrents... 

Other groups of ecdysis Inhibitors act by Inhibiting chltln synthesis. The most prominent of these are the synthetic 2,6-dlhalogenated benzoyl-phenylurea compounds exemplified by the commercial Insecticide, Dlmllln (dlflubenzuron) (Figure 5) (23,... 

Although It Is unknown how azadlrachtln acts as an ecdysis Inhibitor, It apparently does not act by Inhibiting chitln synthetase (32). Possibly, ecdysis Inhibition Is caused by a disruption of the tltre of ecdysterone (40, 44) or by an Interference with the neuroendocrine system, prothoradcotroplc hormone and allatotroplc hormone, which controls the tltres of molting hormone and juvenile hormone, respectively (45). 

Kubo, I. and J. Klocke, Insect ecdysis inhibitors, in Natural Resistance of Plants to Pests (M. B. Green and P. A. Hedin, eds.), ACS Symposium Series 296, 206-219, American Chemical Society, Washington, DC, 1986. 

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). 

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... 

These molecules were shown to be potent inhibitors of chitinase, an enzyme involved in the ecdysis of many insects and crustaceans, whose inhibitors are supposed to control the settlement of barnacles and, therefore, could have a potential application as antifouling agents. Unfortunately, no data are available in the literature about cytotoxic, immunosuppressive, or antibacterial activities of styloguanidines and, thus, a comparison with the potently bioactive congeners palau amines is not possible. 

Another natural product which was Isolated from A. indica and found to have potent ecdysis Inhibitory activity Is deacetyl-azadlrachtlnol (Figure 8) (42). The biological activity of deacetylazadlrachtlnol fed in artificial diet to H. virescens Is shown In Table IV. Although deacetylazadlrachtlnol was about 2.5-fold less active than was azadlrachtln as an Insect growth Inhibitor (EC50 - 0.17 and 0.07 ppm, respectively), the two compounds had the same ecdysis inhibitory activity (EI50 "... 

Allosamidin (2) and its congeners demethylallosamidin (3), methylallosamidin (4), methyl A-demethylallosamidin (5), glucoallosamidin A (6) and glucoallosamidin B (7) are the first examples of endochitinase inhibitors. They were isolated from the mycelial extract of Streptomyces sp. 1713 and related actinomycete SA-684 and A82516. They exhibit the inhibitory activity against the chitinases of the silkworm Bombyx mori in vitro and prevent its larval ecdysis in It has been thought that the chitinase inhibitor would... 

Earlier work investigated growth effects from monoterpenoids dosed topically on last-instar larvae of the house fly (19). Development and metamorphosis failures occurred with several compounds. Cineole was the most active inhibitor of pupal eclosion (40% inhibition at a dose of 10 /lig/insect) and of imaginal differentiation, within those uneclosed pupae. Camphene, eugenol, and a-pinene were also active. Inhibition of pupal ecdysis was highest in insects treated with camphene, although carvone and several others were also effective. 

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