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<p>Epilepsy is a serious brain disease that urgently needs new drugs to treat it. In this study, three new <i>α</i>-pyrone derivatives, nocardipones A − C (<b>1 − 3</b>), were isolated from the sponge-associated actinomycete <i>Nocardiopsis</i> sp. NBUDK19 guided by anti-epileptic bioactivity using an in vivo zebrafish model. Compounds <b>1</b> − <b>3</b> were isolated and purified by silica gel column chromatography combined with semi-preparative HPLC. The structures of <b>1 − 3</b> were elucidated by UV, HRESIMS, NMR spectroscopic analysis, optical rotation, and computational chemical calculations. Our pharmacological study showed that compounds <b>1 − 3</b> exhibited notable reductions in seizure-like locomotor activity at 5 μg/mL. The qPCR analysis showed that compounds <b>1 − 3</b> significantly regulated the mRNA expression levels of <i>c-fos</i> and genes associated with GABAergic-glutamatergic signaling, including <i>gria1b</i> and <i>gat1</i>. The molecular docking revealed that compounds <b>1 − 3</b> strongly binding to 4-aminobutyric acid transaminase, with binding energies of − 7.3, − 7.8, and − 7.3 kcal/mol, respectively. This work enriches bioactive drug discovery to treat epilepsy and illustrates an underlying pharmacological and molecular mechanism of these natural <i>α</i>-pyrones.</p>

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Three New α-Pyrone Derivatives with Antiepileptic Activity from the Marine Actinomycete Nocardiopsis sp. NBUDK19

  • 期刊论文

  • 发表日期：

    2025年5月14日

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  • Jinling Li,
  • Zhiyan Zhou,
  • Fangjian Feng,
  • Wei Yuan,
  • Yawen Zhang,
  • Jiaxing Wang,
  • Bin Zhang,
  • Haixiao Jin,
  • Shan He,
  • Lijian Ding

摘要

Epilepsy is a serious brain disease that urgently needs new drugs to treat it. In this study, three new α-pyrone derivatives, nocardipones A − C (1 − 3), were isolated from the sponge-associated actinomycete Nocardiopsis sp. NBUDK19 guided by anti-epileptic bioactivity using an in vivo zebrafish model. Compounds 1 − 3 were isolated and purified by silica gel column chromatography combined with semi-preparative HPLC. The structures of 1 − 3 were elucidated by UV, HRESIMS, NMR spectroscopic analysis, optical rotation, and computational chemical calculations. Our pharmacological study showed that compounds 1 − 3 exhibited notable reductions in seizure-like locomotor activity at 5 μg/mL. The qPCR analysis showed that compounds 1 − 3 significantly regulated the mRNA expression levels of c-fos and genes associated with GABAergic-glutamatergic signaling, including gria1b and gat1. The molecular docking revealed that compounds 1 − 3 strongly binding to 4-aminobutyric acid transaminase, with binding energies of − 7.3, − 7.8, and − 7.3 kcal/mol, respectively. This work enriches bioactive drug discovery to treat epilepsy and illustrates an underlying pharmacological and molecular mechanism of these natural α-pyrones.