Design and Synthesis of Insect Juvenile Hormone antagonists

昆虫保幼激素拮抗剂的设计与合成

• 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

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，并评价了它们诱导家蚕幼虫早熟变态的活性，已知这是由去除咽侧体或抗保幼激素剂引起的。5-（2-烯丙氧基苯基）-1-辛基咪唑和5-（2-氯苯基）-1-辛基咪唑表现出较高的活性。无论是甲氧普烯，保幼激素（JH）激动剂，也不是虫酰肼，蜕皮激素激动剂，可以完全抵消早熟变态诱导的高剂量的每种化合物，但这两种激素激动剂是必要的完全救援。在测试的3-（1-烯基）吡啶衍生物中，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]吡啶显示最高活性。通过饮食给予20-羟基蜕皮激素，每种化合物诱导的性早熟变态都是完全可逆的，表明这些化合物暂时抑制性早熟变态。 ...更多信息 幼虫血淋巴中蜕皮激素滴度对诱导早熟变态的影响。1-[3-（4-苯氧基苯氧基）丙基]咪唑（KS-175）具有两种昆虫生长调节剂（IGR）的特征结构部分，即保幼激素类似物的苯氧基苯氧基烷基和细胞色素P450抑制剂的咪唑环。KS-175对4龄幼虫外用20多天后，在倒数第二龄（4龄）幼虫中既不蜕皮也不变态。这一活动不同于任何报告的IGR。治疗后，血淋巴中蜕皮激素水平没有增加，前胸腺细胞萎缩。当处理的第4幼虫喂食人工饲料补充剂与20 ppm的20-羟基蜕皮激素，幼虫蜕皮的最终（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不可逆地损害前胸腺中蜕皮激素的生物合成。IPLB-Sf 21 AE II昆虫细胞的生长被低浓度的甲氧普烯显著地促进，表明该细胞系可能具有靶位点样受体以识别JH，随后促进细胞增殖。少

项目成果

Takahiro Shiotsuki: "Effect of 1-(4-phenoxyphenoxypropyl)imidazole(KS-175)on larval growth in the silkworm Bombyx mori." Journal of Insect Physiology. 45(in press). (1999)

Takahiro Shiotsuki：“1-(4-苯氧基苯氧基丙基)咪唑 (KS-175) 对家蚕幼虫生长的影响。”

Nozomu Toyomura: "Effect of tropine derivatives,antimuscarinic agents,on the growth on Bombyx mori larvae." Bioscience Biotechnology and Biochemistry. 62・10. 2046-2048 (1998)

Nozomu Toyomura：“托品衍生物、抗毒蕈碱剂对家蚕幼虫生长的影响。”生物科学生物技术和生物化学 62·10 (1998)。

Takahiro Shiotsuki: "Effect of 1-(4-phenoxyphenoxypropyl)imidazole(KS-175) on larval growth in the silkworm Bombyx mori." Journal of Insect Physiology. 45(in press). (1999)

Takahiro Shiotsuki：“1-(4-苯氧基苯氧基丙基)咪唑 (KS-175) 对家蚕幼虫生长的影响。”

Hiroto Tamura: "Effects of insect hormone related compounds on the growth of insect cells" J.Pesticide Sci. 22. 42-44 (1997)

Hiroto Tamura：“昆虫激素相关化合物对昆虫细胞生长的影响”J.Pesticide Sci。

Takahiro Shiotsuki: "Errect of 1- (4-phenoxy-phenoxyprophl) imidazole (KS-175) on larval growth in the silkworm Bombyx mori." J.Insect Physiol.45 (in press). (1999)

Takahiro Shiotsuki：“1-（4-苯氧基-苯氧基丙酸）咪唑（KS-175）对家蚕幼虫生长的影响。”