Design and Synthesis of Insect Juvenile Hormone antagonists

昆虫保幼激素拮抗剂的设计与合成

基本信息

批准号：
09460029
负责人：
KUWANO Eiichi
金额：
$ 6.53万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09460029/
关键词：
juvenile hormone precocious metamorphosis imidazoles 3-pyridines 変態昆虫培養細胞

项目摘要

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

制备了大量的 1,5-二取代咪唑和 3-(1-烯基)吡啶，并评估了它们诱导家蚕幼虫早熟变态的活性，已知这种早熟变态是由去除体体引起的allata或抗保幼激素剂5-(2-烯丙氧基苯基)-1-辛基咪唑和5-(2-氯苯基)-1-辛基咪唑均表现出相对较高的活性，保幼激素 (JH) 激动剂甲氧普林和蜕皮激素激动剂虫酰肼均不能完全对抗高剂量每种化合物引起的性早熟。在所测试的 3-(1-烯基)吡啶衍生物中，激动剂对于完全救援是必要的。 3-(2-甲基-1-苯基-1-丙烯基)吡啶和3-[(E)-7-(4-乙基苯氧基)-1-甲基-1-庚烯基]吡啶显示出各自诱导的最高变态活性。通过饮食给予 20-羟基蜕皮激素，该化合物是完全可逆的，表明这些化合物暂时降低了幼虫中的蜕皮类固醇滴度1-[3-(4-苯氧基苯氧基)丙基]咪唑 (KS-175)，具有两种类型的昆虫生长调节剂 (IGR) 特征部分：保幼激素类似物的苯氧基苯氧基烷基和咪唑。合成了一种有效的细胞色素 P450 抑制剂，并评估了其对 KS-175 引起的生物活性。当局部施用于第 4 龄幼虫时，倒数第二（第 4）龄幼虫在 20 天内既没有蜕皮也没有变态。这种活性与任何报道的 IGR 不同。当用 20 ppm 的人工饲料补充剂喂养经过治疗的第 4 只幼虫时，前胸腺已经萎缩。 20-羟基蜕皮激素，幼虫蜕皮至最终（第 5 龄）的时间与对照幼虫相似。这些结果表明，局部应用 KS-175 会不可逆地损害前胸腺中的蜕皮激素生物合成。低浓度的甲氧普林显着促进了昆虫细胞的生长，这表明该细胞系可能具有类似受体的靶位点来识别JH其次是促进细胞增殖。