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Abstract <p>Combining antitumor drugs with fluorescent groups to form therapeutic prodrugs has important application value in cancer treatment. In this study, we designed and synthesized a novel anticancer therapeutic prodrug, 2-(benzo[<i>d</i>]thiazol-2-yl)-4-methoxyphenyl 4-{[4-(ergosterol peroxide-3-yl-oxy)-4-oxobutyl]disulfaneyl}butanoate. The synthesis was achieved by covalently linking ergosterol peroxide (EP) and 2-(benzo[<i>d</i>]thiazol-2-yl)-4-methoxyphenol through a disulfide (S–S) bond. The reaction of the prodrug with high-concentration GSH in tumor tissues broke the disulfide bond, dissociating it into free EP and activated fluorescent BTMP, enabling the visual monitoring of the drug. A series of spectral analyses showed that 2-(benzo[<i>d</i>]thiazol-2-yl)-4-methoxyphenyl 4-{[4-(ergosterol peroxide-3-yl-oxy)-4-oxobutyl]disulfaneyl}butanoate could be specifically activated by high-concentration GSH and had good stability. Cytotoxicity assays showed that it had strong inhibitory activity against breast cancer MCF-7 cells but low toxicity toward human normal breast cells (MCF-10A). In addition, it could induce apoptosis and enable visual tracking in MCF-7 cells. Consequently, the specific drug-release behavior of 2-(benzo[<i>d</i>]thiazol-2-yl)-4-methoxyphenyl 4-{[4-(ergosterol peroxide-3-yl-oxy)-4-oxobutyl]disulfaneyl}butanoate within tumors renders it a highly promising prodrug candidate. This approach thus offers a viable strategy for tumor diagnosis and treatment.</p>

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Preparation of Ergosterol Peroxide Prodrug Based on Glutathione Response and Evaluation of Its Antitumor Effect

  • 期刊论文

  • 发表日期：

    2025年4月25日

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  • R. Luo,
  • L. M. Hou,
  • Q. Wang,
  • Y. Lin,
  • S. Q. Deng,
  • L. Wang,
  • M. Bu

摘要

Abstract

Combining antitumor drugs with fluorescent groups to form therapeutic prodrugs has important application value in cancer treatment. In this study, we designed and synthesized a novel anticancer therapeutic prodrug, 2-(benzo[d]thiazol-2-yl)-4-methoxyphenyl 4-{[4-(ergosterol peroxide-3-yl-oxy)-4-oxobutyl]disulfaneyl}butanoate. The synthesis was achieved by covalently linking ergosterol peroxide (EP) and 2-(benzo[d]thiazol-2-yl)-4-methoxyphenol through a disulfide (S–S) bond. The reaction of the prodrug with high-concentration GSH in tumor tissues broke the disulfide bond, dissociating it into free EP and activated fluorescent BTMP, enabling the visual monitoring of the drug. A series of spectral analyses showed that 2-(benzo[d]thiazol-2-yl)-4-methoxyphenyl 4-{[4-(ergosterol peroxide-3-yl-oxy)-4-oxobutyl]disulfaneyl}butanoate could be specifically activated by high-concentration GSH and had good stability. Cytotoxicity assays showed that it had strong inhibitory activity against breast cancer MCF-7 cells but low toxicity toward human normal breast cells (MCF-10A). In addition, it could induce apoptosis and enable visual tracking in MCF-7 cells. Consequently, the specific drug-release behavior of 2-(benzo[d]thiazol-2-yl)-4-methoxyphenyl 4-{[4-(ergosterol peroxide-3-yl-oxy)-4-oxobutyl]disulfaneyl}butanoate within tumors renders it a highly promising prodrug candidate. This approach thus offers a viable strategy for tumor diagnosis and treatment.