| Yazarlar (5) |
Gurbet Çelik Turgut
Türkiye |
|
Furkan Çakır
Bezm-İ Âlem Vakıf Üniversitesi, Türkiye |
|
Alaattin Şen
Türkiye |
Doç. Dr. Feyzi Sinan TOKALI
Kafkas Üniversitesi, Türkiye |
|
Halil Şenol
Bezm-İ Âlem Vakıf Üniversitesi, Türkiye |
| Özet |
| In this study, a novel series of eleven 3,5-disubstituted thiazolidine-2,4-dione (TZD) derivatives were rationally designed and synthesized, incorporating tertiary amine moieties to enhance cholinesterase binding. The acetamide-linked TZD scaffold was selected for its potential dual functionality: cholinesterase inhibition and cytotoxicity against neuronal cells. All compounds were evaluated for their inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), alongside cytotoxicity assays on SH-SY5Y cancerous neuroblastoma and HEK-293 healthy cells. Compound 7 showed the strongest AChE inhibition (IC = 17.87 μM and K = 19.48 μM), while compound 8 exhibited the most potent BChE inhibition (IC = 34.98 μM and K = 26.15 μM), showing better activity than reference inhibitors (IC = 53.81 μM and IC = 43.21 μM). Several compounds, particularly 3, showed the greatest selectivity toward SH-SY5Y cells (SI = 4.9), followed by 8 (SI = 4.4) and 2 (SI = 3.4). All three compounds matched or exceeded Sorafenib's selectivity (SI = 3.8), despite Sorafenib exhibiting stronger cytotoxicity. Molecular docking and dynamics simulations supported the observed in vitro results, revealing strong and stable binding interactions of compound 7 with AChE and compound 8 with BChE. The correlation between BChE inhibition and cytotoxicity suggests potential multifunctionality. The findings highlight compounds 7 and 8 as promising lead candidates for neurodegenerative disorders and support their eligibility for further in-depth pharmacological investigations. |
| Anahtar Kelimeler |
| AChE | BChE | Cholinesterase inhibition | SH-SY5Y | Neurodegenerative disorders |
| Makale Türü | Özgün Makale |
| Makale Alt Türü | SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale |
| Dergi Adı | Bioorganic Chemistry |
| Dergi ISSN | 0045-2068 Wos Dergi Scopus Dergi |
| Dergi Tarandığı Indeksler | SCI-Expanded |
| Dergi Grubu | Q1 |
| Makale Dili | İngilizce |
| Basım Tarihi | 08-2025 |
| Cilt No | 164 |
| Sayı | 108869 |
| Doi Numarası | 10.1016/j.bioorg.2025.108869 |
| Makale Linki | https://doi.org/10.1016/j.bioorg.2025.108869 |
| Atıf Sayıları | |
| WoS | 1 |
