Synthesis of 1,4-benzodioxan derivatives and the evaluation of their biological activity as a novel juvenile hormone signaling inhibitor

BACKGROUNDJuvenile hormone (JH) signaling inhibitors may be used as insect growth regulators because of their ability to control metamorphosis and reproduction in insects by regulating the action of JH.RESULTSWe identified ethyl (E)-3-(4-{[7- (4-methoxycarbonylbenzyloxy)-1,4-benzodioxan-6-yl]methyl}phenyl)prop-2-enoate (EMBP) and observed its strong precocious metamorphosis-inducing activity against silkworm larvae. To further elucidate its mechanism of action, we investigated the effect of EMBP on the JH-mediated signaling pathway in vitro and in vivo. In a reporter assay using a Bombyx mori cell line, EMBP strongly suppressed the induction of reporter gene expression by Juvenile hormone I (JH I) in a concentration-dependent manner. A parallel rightward shift was observed in the dose-response curve of JH I after treatment with EMBP, indicating that EMBP competitively inhibited JH. Moreover, we monitored developmental changes in the JH-responsive gene, Kruppel homolog 1 (Kr-h1), and ecdysone-responsive gene, Broad-Complex (BRC), in EMBP-treated silkworm larvae. EMBP suppressed only the expression of Kr-h1 in third-instar larvae.CONCLUSIONOur results demonstrated that EMBP specifically regulates the JH-mediated Kr-h1 signaling pathway. EMBP could be used as a lead compound in the development of new insect growth regulators. & COPY; 2023 Society of Chemical Industry. EMBP, a novel juvenile hormone (JH) signaling inhibitor, shows precocious metamorphosis-inducing activity against silkworms by specifically inhibiting the expression of Kr-h1, a JH early response gene.image

Automated summary

A novel juvenile hormone (JH) signaling inhibitor, ethyl (E)-3-(4-{[7-(4-methoxycarbonylbenzyloxy)-1,4-benzodioxan-6-yl]methyl}phenyl)prop-2-enoate (EMBP), was discovered to induce precocious metamorphosis in silkworm larvae by specifically inhibiting the expression of Kr-h1, a JH early response gene. This study provides insights into the mechanism of action of EMBP in the JH-mediated signaling pathway and highlights its potential as a lead compound for the development of new insect growth regulators.