| Yazarlar (6) |
Özcan Güleç
|
Doç. Dr. Hatice Esra DURAN
Kafkas Üniversitesi, Türkiye |
|
Mustafa Arslan
Sakarya Üniversitesi, Türkiye |
|
Kübra Gizem Yıldıztekin
Erzincan Binali Yıldırım Üniversitesi, Türkiye |
|
Abdulilah Ece
Türkiye |
|
Cüneyt Türkeş
Erzincan Binali Yıldırım Üniversitesi, Türkiye |
| Özet |
| Aldose reductase (ALR2) has emerged as a dual-function therapeutic target, critically involved in diabetic complications and cancer-related redox adaptation. In this study, a novel series of 15 chalcone-inspired heteroaryl–dihydronaphthalenone hybrids bearing indole, carbazole, or phenothiazine motifs (4a–4f, 8a–8e, 12a–12d) were rationally designed, synthesized, and systematically evaluated for their ALR2 inhibitory and anticancer properties. Enzymatic inhibition assays revealed low-nanomolar to low-nanomolar KI values, with compound 8b (KI = 3.59 nM, pKI = 8.44) emerging as the most potent inhibitor, outperforming the reference drug Epalrestat. SAR analysis highlighted the critical role of flexible alkyl side chains and polycyclic aromatic scaffolds in optimizing hydrophobic anchoring. Complementary in silico studies, including MM-GBSA binding energy calculations (ΔGbind = −56.37 kcal/mol … |
| Anahtar Kelimeler |
| ALR2 inhibition | Indole hybrids | Carbazole derivatives | Phenothiazine scaffold | Diabetic complications | Oxidative stress | Dual-action inhibitors | Molecular docking | Quantum descriptors | Molecular dynamics | cancer redox biology |
| 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 | Türkçe |
| Basım Tarihi | 09-2025 |
| Cilt No | 164 |
| Doi Numarası | 10.1016/j.bioorg.2025.108861 |
| Makale Linki | https://doi.org/10.1016/j.bioorg.2025.108861 |
| Atıf Sayıları | |
| WoS | 10 |
| Google Scholar | 14 |
