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<p>This study investigates the synthesis, biological evaluation, and computational profiling of novel syringaldehyde-based triarylpyridine derivatives (TAP1–TAP4) as potential dual-action agents against colorectal cancer (CRC) and bacterial biofilms. The studied compounds demonstrated significant antiproliferative effects on HCT116 colon cancer cells, with TAP2 exhibiting an IC<sub>50</sub> of 5.6&#xa0;µg/mL at 48&#xa0;h. Further mechanistic studies revealed that TAP2 and TAP3 upregulate caspase-3, caspase-8, and caspase-9, indicating activation of both intrinsic and extrinsic apoptotic pathways. Additionally, these compounds effectively inhibited <i>Escherichia coli</i> biofilm formation and quorum sensing (QS), with TAP2 reducing biofilm activity by 60.61%. To understand the structure–activity relationship, a comprehensive computational framework, including density functional theory (DFT) calculations, MEP, ELF, LOL, and ALIE analysis, was employed. These studies elucidated substituent-driven electronic properties, which correlated with the observed biological activities and molecular docking interactions. Docking studies identified the TAP3 compound as a potent JAK2 inhibitor and TAP2 as a strong binder of EGFR/CDK9. ADME predictions indicated moderate lipophilicity and intestinal absorption for TAP2, though structural refinements are necessary to address solubility and toxicity concerns. Overall, these syringaldehyde-triarylpyridine hybrids offer a promising strategy for CRC treatment by combining anticancer and antibiofilm properties. This integrated approach provides a robust foundation for future structural optimization, positioning these derivatives as compelling lead candidates for advanced therapeutic applications, especially in cases involving microbial dysbiosis.</p>

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Comprehensive in silico and experimental study of syringaldehyde-triarylpyridine hybrids as dual-action anticancer and antibiofilm agents

  • 期刊论文

  • 发表日期：

    2025年10月11日

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  • Aysegul Akkoyunlu,
  • Ahmad Badreddin Musatat,
  • Ilker Kiliccioglu,
  • Gorkem Dulger,
  • Esra Nur Albayrak,
  • Alparslan Atahan

摘要

This study investigates the synthesis, biological evaluation, and computational profiling of novel syringaldehyde-based triarylpyridine derivatives (TAP1–TAP4) as potential dual-action agents against colorectal cancer (CRC) and bacterial biofilms. The studied compounds demonstrated significant antiproliferative effects on HCT116 colon cancer cells, with TAP2 exhibiting an IC50 of 5.6 µg/mL at 48 h. Further mechanistic studies revealed that TAP2 and TAP3 upregulate caspase-3, caspase-8, and caspase-9, indicating activation of both intrinsic and extrinsic apoptotic pathways. Additionally, these compounds effectively inhibited Escherichia coli biofilm formation and quorum sensing (QS), with TAP2 reducing biofilm activity by 60.61%. To understand the structure–activity relationship, a comprehensive computational framework, including density functional theory (DFT) calculations, MEP, ELF, LOL, and ALIE analysis, was employed. These studies elucidated substituent-driven electronic properties, which correlated with the observed biological activities and molecular docking interactions. Docking studies identified the TAP3 compound as a potent JAK2 inhibitor and TAP2 as a strong binder of EGFR/CDK9. ADME predictions indicated moderate lipophilicity and intestinal absorption for TAP2, though structural refinements are necessary to address solubility and toxicity concerns. Overall, these syringaldehyde-triarylpyridine hybrids offer a promising strategy for CRC treatment by combining anticancer and antibiofilm properties. This integrated approach provides a robust foundation for future structural optimization, positioning these derivatives as compelling lead candidates for advanced therapeutic applications, especially in cases involving microbial dysbiosis.