Scholarlink

<p>Cancer continues to be a leading cause of global mortality, highlighting the ongoing need for novel anticancer compounds that offer high efficacy with improved side effect profiles. In the present study, a series of 3<i>H</i>-1,2-dithiole-3-thione derivatives (<b>DTT-S1-18</b>) were synthesized as promising anticancer agents, and the structures of products were confirmed by spectral techniques. H<sub>2</sub>S-releasing experiments showed that most of the compounds released higher amounts of H<sub>2</sub>S slowly over time compared to standard <b>ADT-OH</b>. All compounds were tested for antiproliferative activity on HT-29, PC-3, MCF-7, and HUVEC cell lines. Compounds <b>DTT-S6</b> (3-nitrophenyl derivative) and <b>DTT-S8</b> (methionine derivative) have the lowest IC<sub>50</sub> values of 41.6 and 38.9 µM on the MCF-7 cell line, respectively. Based on the wound healing and colony formation assays performed in MCF-7 cells, the wound areas were not significantly changed after treatment with compounds <b>DTT-S6</b> and <b>DTT-S8</b>, whereas compound <b>DTT-S8</b> at double IC<sub>50</sub> dose inhibited colony formation by 81.82%. In addition, molecular docking, MD simulations, MM/GBSA binding free energy calculations, and binary QSAR analyses were performed to explore the potential target interactions and predicted activity profiles of the synthesized compounds toward inflammation-related proteins, including COX-1, COX-2, 5-LOX, and iNOS, thereby supporting the development of mechanistic hypotheses for future validation. Furthermore, structure–activity relationship (SAR) analyses were conducted to correlate the structural characteristics of the synthesized compounds with their H<sub>2</sub>S releasing potential and biological profiles. Overall, this work integrates experimental anticancer evaluation with computational pathway and structure-based cancer/inflammation analyses to characterize novel DTT-based H<sub>2</sub>S donors. The findings identify particularly compound <b>DTT-S8</b>, as a promising in vitro anticancer candidate, while the computational results suggest a putative involvement of inflammation-related targets, particularly the COX-2/5-LOX axis, which requires direct biochemical and cellular validation.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

New 3H-1,2-Dithiole-3-thione derivatives: Design and synthesis, H2S-release profile, in vitro anticancer activity, and in silico multi-target assessment

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月26日

查看全文
  • Semra Altunsoy,
  • Yakup Berkay Yılmaz,
  • Tuğba Güngör,
  • Hazal Nazlıcan Atalay,
  • Mine Isaoğlu,
  • Serdar Durdağı,
  • Mehmet Ay,
  • Tugba Boyunegmez Tumer

摘要

Cancer continues to be a leading cause of global mortality, highlighting the ongoing need for novel anticancer compounds that offer high efficacy with improved side effect profiles. In the present study, a series of 3H-1,2-dithiole-3-thione derivatives (DTT-S1-18) were synthesized as promising anticancer agents, and the structures of products were confirmed by spectral techniques. H2S-releasing experiments showed that most of the compounds released higher amounts of H2S slowly over time compared to standard ADT-OH. All compounds were tested for antiproliferative activity on HT-29, PC-3, MCF-7, and HUVEC cell lines. Compounds DTT-S6 (3-nitrophenyl derivative) and DTT-S8 (methionine derivative) have the lowest IC50 values of 41.6 and 38.9 µM on the MCF-7 cell line, respectively. Based on the wound healing and colony formation assays performed in MCF-7 cells, the wound areas were not significantly changed after treatment with compounds DTT-S6 and DTT-S8, whereas compound DTT-S8 at double IC50 dose inhibited colony formation by 81.82%. In addition, molecular docking, MD simulations, MM/GBSA binding free energy calculations, and binary QSAR analyses were performed to explore the potential target interactions and predicted activity profiles of the synthesized compounds toward inflammation-related proteins, including COX-1, COX-2, 5-LOX, and iNOS, thereby supporting the development of mechanistic hypotheses for future validation. Furthermore, structure–activity relationship (SAR) analyses were conducted to correlate the structural characteristics of the synthesized compounds with their H2S releasing potential and biological profiles. Overall, this work integrates experimental anticancer evaluation with computational pathway and structure-based cancer/inflammation analyses to characterize novel DTT-based H2S donors. The findings identify particularly compound DTT-S8, as a promising in vitro anticancer candidate, while the computational results suggest a putative involvement of inflammation-related targets, particularly the COX-2/5-LOX axis, which requires direct biochemical and cellular validation.