Akkoyunlu, AysegulMusatat, Ahmad BadreddinKiliccioglu, IlkerDulger, GorkemAlbayrak, Esra NurAtahan, Alparslan2026-07-012026-07-0120251040-04001572-9001https://doi.org/10.1007/s11224-025-02634-zhttps://hdl.handle.net/20.500.12684/23667This 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 mu g/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.en10.1007/s11224-025-02634-zinfo:eu-repo/semantics/closedAccessTriarylpyridineSyringaldehydeAntibiofilmColon CancerIn SilicoArticle2-s2.0-105018615085WOS:001590887100001Q2Q20000-0002-3663-74120000-0002-4137-49010000-0003-3367-9665