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<p><i>Mycobacterium marinum</i> can cause disease in both human beings and fishes. Infected fish exhibits symptoms commonly referred to as fish tuberculosis. In this research, we screened a 14-Membered Resorcylic Acid Lactones (RALs) library constructed in the laboratory for <i>in vitro</i> anti-<i>Mycobacterium marinum</i> activity and found that several compounds, including compounds <b>3</b>, <b>4</b>, <b>6</b>, <b>10</b>, and <b>17</b>–<b>26</b>, showed good activity. Notably, the trace natural product cochilimycin B (compound <b>3</b>) possesses significant long-lasting inhibitory function to <i>Mycobacterium marinum</i>. It also shows synergistic effects with drugs like isoniazid, ethambutol, and bedaquiline (<i>FICI</i>≤0.5). In addition, cochilimycin B showed a significant inhibitory effect on the biofilm produced by <i>Mycobacterium marinum</i>, with an inhibition rate of 65.9%. To solve the bottleneck problem of natural product drug sources, we realized an efficient one-step semi-synthetic method to obtain compound <b>3</b> with a yield of 32.1%. <i>In vivo</i>, inflammatory changes in BALB/c mice infected with <i>Mycobacterium marinum</i> were characterized. After 12 h of infection, IL-1<i>β</i> was 20%–30% lower in the spleen and tail of the <b>3</b>-treated group compared to the control group. In the thymus and tail of the treated group, TNF-<i>α</i> levels were 30%–60% lower than in the control group. This is the first time that the significant anti-<i>Mycobacterium marinum</i> effect of cochilimycin B from 14-Membered Resorcylic Acid Lactones (14-RALs) was reported, offering a new chemical molecule for anti-<i>Mycobacterium marinum</i> drug research.</p>

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Cochilimycin B Is a Potential Anti-Mycobacterium marinum Medicine Through Screening the 14-Membered Resorcylic Acid Lactones Library

  • 期刊论文

  • 发表日期：

    2025年12月8日

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  • Qianqian Jing,
  • Yajie Cheng,
  • Wenhui Wang,
  • Junna Yin,
  • Meiyan Wei,
  • Tongyi Xu,
  • Changlun Shao

摘要

Mycobacterium marinum can cause disease in both human beings and fishes. Infected fish exhibits symptoms commonly referred to as fish tuberculosis. In this research, we screened a 14-Membered Resorcylic Acid Lactones (RALs) library constructed in the laboratory for in vitro anti-Mycobacterium marinum activity and found that several compounds, including compounds 3, 4, 6, 10, and 17–26, showed good activity. Notably, the trace natural product cochilimycin B (compound 3) possesses significant long-lasting inhibitory function to Mycobacterium marinum. It also shows synergistic effects with drugs like isoniazid, ethambutol, and bedaquiline (FICI≤0.5). In addition, cochilimycin B showed a significant inhibitory effect on the biofilm produced by Mycobacterium marinum, with an inhibition rate of 65.9%. To solve the bottleneck problem of natural product drug sources, we realized an efficient one-step semi-synthetic method to obtain compound 3 with a yield of 32.1%. In vivo, inflammatory changes in BALB/c mice infected with Mycobacterium marinum were characterized. After 12 h of infection, IL-1β was 20%–30% lower in the spleen and tail of the 3-treated group compared to the control group. In the thymus and tail of the treated group, TNF-α levels were 30%–60% lower than in the control group. This is the first time that the significant anti-Mycobacterium marinum effect of cochilimycin B from 14-Membered Resorcylic Acid Lactones (14-RALs) was reported, offering a new chemical molecule for anti-Mycobacterium marinum drug research.