Design and Synthesis of Insect Juvenile Hormone antagonists

点击翻译按钮获取中文摘要

A large number of 1,5-disubstituted imidazoles and 3-(1-alkenyl)pyridines were prepared and evaluated for their activity to induce precocious metamorphosis in larvae of the silkworm, Bombyx mori, which is known to be caused by removal of the corpora allata or anti-juvenile hormone agents. 5-(2-Allyloxyphenyl)- 1 -octylimidazole and 5-(2-chlorophenyl)- 1 -octylimidazole showed relatively high activity. Neither methoprene, a juvenile hormone (JH) agonist, nor tebufenozide, an ecdysteroid agonist, could fully counteract precocious metamorphosis induced by high doses of each compound, but both hormone agonists were necessary for complete rescue. Among the 3-(1-alkenyl) pyridine derivatives tested, 3-(2-methyl-1-phenyl-1-propenyl) pyridine and 3-[(E)-7-(4-ethylphenoxy)-1-methyl-1-heptenyl] pyridine showed highest activity. Precocious metamorphosis induced by each compound was fully reversible by dietary administration of 20-hydroxyecdysone, indicating that these compounds temporarily depres … More s the ecdysteroid titer in the larval hemolymph to induce precocious metamorphosis. 1-[3-(4-Phenoxyphenoxy) propyl] imidazole (KS-175), which has two types of characteristic moieties of insect growth regulators (IGRs), a phenoxyphenoxyalkyl group of juvenile hormone analogs and an imidazole ring as a potent cytochrome P450 inhibitor, was synthesized and evaluated for its biological activity on the silkworm. KS-175 caused neither molting nor metamorphosis in the penultimate (4th) instar for more than 20 days when applied topically to the 4th instar larvae. This activity was different from any reported IGRs. After the treatment, ecdysteroid levels in hemolymph did not increase and the cells of the prothoracic gland had shrunk. When the treated 4th larvae were fed on artificial diet supplement with 20 ppm of 20-hydroxyecdysone, the larvae molted to the ultimate (5th) instar with a timing similar to that of control larvae. These results suggest that topical application of KS-175 irreversibly damages ecdysone biosynthesis in prothoracic glands. The growth of IPLB-Sf2l AE II insect cells was markedly promoted by a low concentration of methoprene, suggesting that this cell line may have a target site like receptor to recognize the JH followed by the promotion of cell proliferation. Less