Comprehensive in silico and experimental study of syringaldehyde-triarylpyridine hybrids as dual-action anticancer and antibiofilm agents
Küçük Resim Yok
Tarih
2025
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Springer/Plenum Publishers
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
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 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.
Açıklama
Anahtar Kelimeler
Triarylpyridine, Syringaldehyde, Antibiofilm, Colon Cancer, In Silico
Kaynak
Structural Chemistry
WoS Q Değeri
Q2
Scopus Q Değeri
Q2
