Phthalimide–benzoic acid hybrids as potent aldose reductase inhibitors: Synthesis, enzymatic kinetics, and in silico characterization
Yazarlar (7)
Dafina Hoti
Arleta Rifati Nixha
Doç. Dr. Hatice Esra DURAN Kafkas Üniversitesi, Türkiye
Prof. Dr. Mustafa Arslan Sakarya Üniversitesi, Türkiye
Abdulilah Ece Türkiye
Prof. Dr. Cüneyt Türkeş Erzincan Binali Yıldırım Üniversitesi, Türkiye
| Makale Türü | Özgün Makale (SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale) | ||
| Dergi Adı | BIOORGANIC & MEDICINAL CHEMISTRY (Q1) | ||
| Dergi ISSN | 0968-0896 Dergi Bilgileri (2025) | ||
| Dergi Tarandığı Indeksler | SCI-Expanded | ||
| Makale Dili | Türkçe | Basım Tarihi | 12-2025 |
| Cilt / Sayı / Sayfa | 131 / 0 / 118416–0 | DOI | 10.1016/j.bmc.2025.118416 |
| Makale Linki | https://doi.org/10.1016/j.bmc.2025.118416 | ||
| UAK Araştırma Alanları |
Tıbbi Biyokimya
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| 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 |
BM Sürdürülebilir Kalkınma Amaçları
| Atıf Sayıları | |
| Web of Science | 45 |
| Google Scholar | 50 |