N-substituted phthalimide–carboxylic acid hybrids as dual-targeted aldose reductase inhibitors: Synthesis, mechanistic insights, and cancer-relevant profiling
Yazarlar (7)
Blinera Zognjani
Arleta Rifati Nixha
Doç. Dr. Hatice Esra DURAN Kafkas Üniversitesi, Türkiye
Prof. Dr. Mustafa Arslan Sakarya Üniversitesi, Türkiye
Abdulilah Ece
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 CHEMISTRY (Q1) | ||
| Dergi ISSN | 0045-2068 Dergi Bilgileri (2025) | ||
| Dergi Tarandığı Indeksler | SCI-Expanded | ||
| Makale Dili | Türkçe | Basım Tarihi | 08-2025 |
| Cilt / Sayı / Sayfa | 163 / 0 / 108788–0 | DOI | 10.1016/j.bioorg.2025.108788 |
| Makale Linki | https://doi.org/10.1016/j.bioorg.2025.108788 | ||
| UAK Araştırma Alanları |
Tıbbi Biyokimya
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| Özet |
| Aldose reductase (ALR2; AKR1B1), a NADPH-dependent cytosolic oxidoreductase, plays a central role in the polyol pathway and is implicated in hyperglycemia-induced tissue injury. Beyond its metabolic function, elevated ALR2 expression has been reported in several malignancies, including hepatocellular and pulmonary carcinomas, highlighting its potential as a therapeutic target in metabolic-oncologic interface. In this study, a novel set of eleven N-substituted phthalimide–carboxylic acid derivatives (5a–5k) was synthesized and evaluated for ALR2 inhibition, pharmacokinetic characteristics, and cancer-selective safety. Among the series, compound 5f demonstrated the highest inhibitory potency (KI = 7.34 nM), outperforming epalrestat (KI = 232.1 nM). Glide docking positioned 5f within the ALR2 active site (GlideScore: −6.71 kcal/mol), stabilized via key contacts with Tyr48, His110, and Cys298, along … |
| Anahtar Kelimeler |
| Aldose reductase inhibitors | Polyol pathway modulation | N -substituted phthalimides | Structure-activity-energy relationship | Molecular docking and MM-GBSA | Protein-protein interaction | Lead optimization |
BM Sürdürülebilir Kalkınma Amaçları
| Atıf Sayıları | |
| Web of Science | 64 |
| Google Scholar | 68 |