| Yazarlar (6) |
Doç. Dr. Erbay KALAY
Kafkas Üniversitesi, Türkiye |
Yeliz Demir
Ardahan Üniversitesi, Türkiye |
|
Cüneyt Türkeş
Erzincan Binali Yıldırım Üniversitesi, Türkiye |
|
Osman Nuri Aslan
Atatürk Üniversitesi, Türkiye |
|
Esra Pezik
Erzincan Binali Yıldırım Üniversitesi, Türkiye |
|
Engin Şahin
Türkiye |
| Özet |
| Aldose reductase (ALR2), a key enzyme in the polyol pathway, plays a significant role in the onset and progression of diabetic complications, rendering it a critical pharmacological target. In this study, a novel series of twenty-four sulfonate ester-functionalized rhodanine derivatives (compounds 1-24) were rationally designed, synthesized via Knoevenagel condensation, and comprehensively evaluated for their inhibitory activity against ALR2. Spectroscopic and spectrometric methods confirmed the structural integrity of the synthesized compounds. In vitro enzyme inhibition assays revealed that all compounds acted as competitive inhibitors, with several analogues, particularly compounds 6 and 8, exhibiting stronger ALR2 inhibition (K = 0.43 µM and 0.48 µM, respectively) than the reference drug epalrestat (K = 0.98 µM). Structure-activity relationship (SAR) analysis highlighted the critical influence of para-substituted electron-donating (e.g., methyl) and electron-withdrawing (e.g., nitro, halogen) groups on binding potency. Molecular docking of the most potent inhibitor (compound 6) demonstrated a stable binding pose supported by key interactions, including hydrogen bonding with His110 and π-π stacking with Phe122. In silico ADME profiling confirmed favorable drug-likeness properties for all derivatives. Cytotoxicity studies on L929, A549, and RG-2 cell lines revealed that most compounds were less toxic than the reference drug at lower concentrations, with compound 8 showing a promising cytotoxic profile. These findings position rhodanine-sulfonate hybrids as promising scaffolds for the development of next-generation ALR2 inhibitors for the treatment of diabetic complications. |
| Anahtar Kelimeler |
| Rhodanine | Sulfonate ester | Aldose reductase | Cytotoxicity | Molecular docking |
| Makale Türü | Özgün Makale |
| Makale Alt Türü | SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale |
| Dergi Adı | MOLECULAR DIVERSITY |
| Dergi ISSN | 1381-1991 Wos Dergi Scopus Dergi |
| Dergi Tarandığı Indeksler | SCI-Expanded |
| Dergi Grubu | Q2 |
| Makale Dili | İngilizce |
| Basım Tarihi | 01-2025 |
| Doi Numarası | 10.1007/s11030-025-11387-0 |
| Makale Linki | https://link.springer.com/content/pdf/10.1007/s11030-025-11387-0.pdf |
| Atıf Sayıları |
