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

Abstract

BACKGROUNDJuvenile 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.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 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.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.This article is protected by copyright. All rights reserved.