| Yazarlar (5) |
Doç. Dr. Feyzi Sinan TOKALI
Kafkas Üniversitesi, Türkiye |
Halil Şenol
Bezm-İ Âlem Vakıf Üniversitesi, Türkiye |
|
Şeyma Ateşoğlu
Bezm-İ Âlem Vakıf Üniversitesi, Türkiye |
|
Pelin Tokalı
|
|
Fahri Akbaş
Bezm-İ Âlem Vakıf Üniversitesi, Türkiye |
| Özet |
| To design, synthesize, and evaluate a series of thiosemicarbazone and thiazolidin-4-one hybrids bearing arylsulfonate groups as potential androgen receptor-targeted anticancer agents. The compounds were synthesized via sequential sulfonylation, thiosemicarbazone formation, and cyclization to thiazolidin-4-ones. The structures of the compounds were characterized using NMR (H and C), FTIR, and HRMS spectroscopic techniques. cytotoxicity was assessed against prostate cancer (PC3) and human umbilical vein endothelial cell lines (HUVEC) using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Molecular docking and MM-GBSA calculations were performed to predict binding affinities toward the androgen receptor. Molecular dynamics simulations (250 ns) were conducted to evaluate the stability and dynamics of the ligand - protein complexes. Thiazolidin-4-one derivatives, particularly compound 9, exhibited potent cytotoxicity (IC = 6.35 µM) and high selectivity (SI = 6.05) over HUVEC cells. Docking and MM-GBSA analyses revealed strong interactions with key residues His-874, Met-742, Trp-741, and Arg-752. MD simulations confirmed minimal deviation from the docking pose (0.75 Å), low RMSD/RMSF values, and persistent hydrogen-bonding networks, supporting the structural stability and binding affinity observed . Structure-activity relationship (SAR) analysis indicated that scaffold cyclization and appropriate arylsulfonate substitution enhance receptor engagement and selectivity. The combined synthetic, computational, and biological results demonstrate that thiazolidin-4-one-based hybrids, particularly compound 9, are promising selective androgen receptor-targeted anticancer agents, warranting further optimization and development. |
| Anahtar Kelimeler |
| Thiosemicarbazone | thiazolidine-4-one | prostate cancer | PC3 | androgen receptor |
| Makale Türü | Özgün Makale |
| Makale Alt Türü | SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale |
| Dergi Adı | Future Medicinal Chemistry |
| Dergi ISSN | 1756-8919 Wos Dergi Scopus Dergi |
| Dergi Tarandığı Indeksler | SCI-Expanded |
| Dergi Grubu | Q2 |
| Makale Dili | İngilizce |
| Basım Tarihi | 11-2025 |
| Cilt No | 17 |
| Sayı | 24 |
| Sayfalar | 2975 / 2986 |
| DOI Numarası | 10.1080/17568919.2025.2592533 |
| Makale Linki | https://doi.org/10.1080/17568919.2025.2592533 |
| Atıf Sayıları | |
| WoS | 2 |
