Fluorenyl-phthalimide hybrids as potent aldose reductase inhibitors with selective anticancer activity: Rational design, synthesis, and molecular insights
Yazarlar (5)
Saliha Gündoğdu
Doç. Dr. Hatice Esra DURAN Kafkas Üniversitesi, Türkiye
Prof. Dr. Mustafa Arslan Sakarya Üniversitesi, Türkiye
Öğr. Gör. Büşra Demir Çetinkaya 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 | 08-2025 |
| Cilt / Sayı / Sayfa | 163 / 0 / 108689–0 | DOI | 10.1016/j.bioorg.2025.108689 |
| Makale Linki | https://doi.org/10.1016/j.bioorg.2025.108689 | ||
| UAK Araştırma Alanları |
Tıbbi Biyokimya
|
||
| Özet |
| Metabolic reprogramming in cancer cells creates actionable vulnerabilities for precision oncology. Aldose reductase (ALR2, AKR1B1; EC 1.1.1.21), a cytosolic NADPH-dependent oxidoreductase, has emerged as a multifunctional player in tumor progression, drug resistance, and oxidative stress modulation, yet remains underexploited as a cancer target. In this study, we report the rational design, synthesis, and biological evaluation of a focused series of fluorenyl-phthalimide carboxylic-acid hybrids (5a-5 l) as dual-acting agents with selective anticancer potential and potent ALR2 inhibition. Among them, compound 5a exhibited the strongest ALR2 inhibition with a KI of 8.71 ± 0.81 nM, far surpassing the clinical comparator epalrestat (KI = 232.10 ± 14.42 nM). In MCF-7 and A549 carcinoma cells, 5a demonstrated moderate antiproliferative activity (IC50 = 52.04 μM and 192.91 μM, respectively) while … |
| Anahtar Kelimeler |
| Aldose reductase inhibitors | Fluorenyl-phthalimide hybrids | Rational drug design | Targeted therapy | Selective cytotoxicity | Precision oncology | Machine learning |
BM Sürdürülebilir Kalkınma Amaçları
| Atıf Sayıları | |
| Web of Science | 65 |
| Google Scholar | 69 |