| Yazarlar (6) |
Ebru Nur Ay
Türkiye |
|
Furkan Çakır
Bezm-İ Âlem Vakıf Üniversitesi, Türkiye |
|
Sarehan Akyüz
|
|
Namık Kılınç
Türkiye |
Doç. Dr. Feyzi Sinan TOKALI
Kafkas Üniversitesi, Türkiye |
|
Halil Şenol
Bezm-İ Âlem Vakıf Üniversitesi, Türkiye |
| Özet |
| In this study, sixteen novel 1,2,3-triazole-substituted salicylic acid phenolic-hydrazone hybrids were synthesized and characterized using NMR, IR, HRMS, and HPLC techniques. The compounds were evaluated for their anticancer potential against HCT-116, Caco-2 and HT-29 colorectal carcinoma cells and normal BEAS-2B epithelial cells. Among them, compound 10k exhibited potent antiproliferative effects on HCT-116, Caco-2 and HT-29 with IC values of 6.84, 10.21, and 9.47 μM, respectively, which were significantly lower than the reference drug sorafenib (IC = 18.25, 13.80 and 7.89 μM) for HTC-116 and Caco-2. Biological assays demonstrated that 10k effectively downregulated TGF-β2 receptor and cytokine expression in a dose-dependent manner, indicating its role in modulating the TGF-β signaling pathway. Apoptosis analysis suggested that cytotoxicity was mediated via non-apoptotic mechanisms. Molecular docking studies revealed a strong binding affinity for compound 10k with a docking score of -11.28 kcal/mol. Furthermore, 250 ns molecular dynamics simulations confirmed the stability of the ligand-receptor complex with an RMSD value stabilized around 1.15 Å. Key interactions included hydrogen bonds with Asn-332, π-π stacking, and halogen bonding. ADMET predictions confirmed favorable drug-like properties with good permeability and safety profiles. These findings position compound 10k as a promising lead candidate for colorectal cancer therapy, targeting TGF-β2 mediated pathways with high efficacy and selectivity. |
| Anahtar Kelimeler |
| 1,2.3-Triazoles | Hydrazone | Colorectal cancer | TGF-beta 2 | Molecular docking |
| Makale Türü | Özgün Makale |
| Makale Alt Türü | SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale |
| Dergi Adı | European Journal of Medicinal Chemistry |
| Dergi ISSN | 0223-5234 Wos Dergi Scopus Dergi |
| Dergi Tarandığı Indeksler | SCI-Expanded |
| Dergi Grubu | Q1 |
| Makale Dili | İngilizce |
| Basım Tarihi | 06-2025 |
| Cilt No | 296 |
| Sayı | 117915 |
| Doi Numarası | 10.1016/j.ejmech.2025.117915 |
| Makale Linki | https://doi.org/10.1016/j.ejmech.2025.117915 |
| Atıf Sayıları | |
| WoS | 2 |
