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

BACKGROUND

Juvenile hormone (JH) signaling inhibitors may be used as insect growth regulators due to their ability to control metamorphosis and reproduction in insects by regulating the action of JH.

RESULTS

We 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 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 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 the developmental changes in the JH‐responsive gene, Krüppel 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.

CONCLUSION

Our 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.

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