| Yazarlar (7) |
Dafina Hoti
|
|
Arleta Rifati Nixha
|
Doç. Dr. Hatice Esra DURAN
Kafkas Üniversitesi, Türkiye |
|
Mustafa Arslan
Sakarya Üniversitesi, Türkiye |
|
Kübra Gizem Yıldıztekin
Türkiye |
|
Abdulilah Ece
Türkiye |
|
Cüneyt Türkeş
Erzincan Binali Yıldırım Üniversitesi, Türkiye |
| Özet |
| Aldose reductase (ALR2; AKR1B1) is implicated in hyperglycemia-driven tissue injury and remains a tractable enzymatic target. We developed a concise, chromatography-free two-step route to phthalimide–benzoic acid hybrids (5a–5m) and profiled their biochemical activity against human ALR2. Across the series, halogenated analogs were most active, with the para-bromophenyl derivative 5d emerging as the top hit (KI = 7.56 nM). Steady-state kinetic analysis indicated a competitive inhibition mechanism. Molecular docking to the ALR2 active site (PDB 4JIR), supported by MM-GBSA rescoring, yielded a catalytically consistent binding mode featuring hydrogen-bonding within the anion-binding region (Tyr48, His110) and complementary hydrophobic contacts (Trp111, Trp219), with Cys298 contributing as a proximal hydrophobic contact. In cell-based assays (A549, Hep3B, L929), the compounds generally … |
| Anahtar Kelimeler |
| Phthalimide-benzoic acid hybrids | Structure-activity relationship (SAR) | Enzyme kinetics (competitive inhibition) | Molecular docking | MM-GBSA binding energy | ADME/Tox prediction | Diabetic complications / polyol pathway |
| Makale Türü | Özgün Makale |
| Makale Alt Türü | SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale |
| Dergi Adı | Bioorganic & Medicinal Chemistry |
| Dergi ISSN | 0968-0896 Wos Dergi Scopus Dergi |
| Dergi Tarandığı Indeksler | SCI |
| Dergi Grubu | Q1 |
| Makale Dili | Türkçe |
| Basım Tarihi | 12-2025 |
| Cilt No | 131 |
| Doi Numarası | 10.1016/j.bmc.2025.118416 |
| Makale Linki | https://doi.org/10.1016/j.bmc.2025.118416 |
| Atıf Sayıları | |
| WoS | 1 |
| Google Scholar | 2 |
