Chalcone-inspired indole, carbazole, and phenothiazine hybrids as potent aldose reductase inhibitors with selective anticancer potential: Rational design, synthesis, and multi-level characterization
Yazarlar (6)
Özcan Güleç
Doç. Dr. Hatice Esra DURAN Kafkas Üniversitesi, Türkiye
Prof. Dr. Mustafa Arslan Sakarya Üniversitesi, Türkiye
Dr. Öğr. Üyesi Kübra Gizem Yıldıztekin Erzincan Binali Yıldırım 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 CHEMISTRY (Q1) | ||
| Dergi ISSN | 0045-2068 Dergi Bilgileri (2025) | ||
| Dergi Tarandığı Indeksler | SCI-Expanded | ||
| Makale Dili | Türkçe | Basım Tarihi | 09-2025 |
| Cilt / Sayı / Sayfa | 164 / 0 / 108861–0 | DOI | 10.1016/j.bioorg.2025.108861 |
| Makale Linki | https://doi.org/10.1016/j.bioorg.2025.108861 | ||
| UAK Araştırma Alanları |
Tıbbi Biyokimya
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| 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 |
BM Sürdürülebilir Kalkınma Amaçları
| Atıf Sayıları | |
| Web of Science | 60 |
| Google Scholar | 65 |