Threonyl-tRNA Synthetase Is the Target of Borrelidin Insecticidal Activity against Silkworms.

IF 3.6 2区生物学 Q2 CHEMISTRY, MEDICINAL

Journal of Natural Products Pub Date : 2025-09-22 DOI:10.1021/acs.jnatprod.5c00737

Aoi Kimishima, Yukihiro Asami, Naozumi Kondo, Sota Negami, Sota Honma, Yukiko Ujie

引用次数: 0

Abstract

We explore borrelidin and semisynthetic derivatives as promising pesticide candidates targeting threonyl-tRNA synthetase (ThrRS). Enzymatic inhibition assays and pull-down assays supported ThrRS as the target of borrelidins for insecticidal activity. Interestingly, derivative 6 showed weak in vitro inhibition but comparable in vivo insecticidal activity to borrelidin. Comparative efficacy tests via intravenous (i.v.) and intraperitoneal (i.p.) administration in silkworm larvae indicated improved pharmacokinetics for compound 6. These findings highlight ThrRS as a valuable insecticidal target and demonstrate the effectiveness of our original silkworm-based screening platform in identifying lead compounds with favorable pharmacokinetics that are often overlooked by conventional in vitro screening approaches.

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Borrelidin对家蚕杀虫活性的作用靶点：苏酰trna合成酶。

我们探索borrelidin及其半合成衍生物作为靶向苏酰trna合成酶（ThrRS）的有前途的农药候选物。酶抑制实验和拉下实验支持ThrRS作为borreliin杀虫活性的靶标。有趣的是，衍生物6的体外抑制作用较弱，但体内杀虫活性与borrelidin相当。通过家蚕幼虫静脉注射和腹腔注射的药效对比试验表明，化合物6的药代动力学得到改善。这些发现突出了ThrRS作为一个有价值的杀虫靶点，并证明了我们基于蚕的原始筛选平台在识别具有良好药代动力学的先导化合物方面的有效性，这些先导化合物通常被传统的体外筛选方法所忽视。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Natural Products 生物-药学

CiteScore

9.10

自引率

5.90%

发文量

294

审稿时长

2.3 months

期刊介绍： The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin. When new compounds are reported, manuscripts describing their biological activity are much preferred. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.