Structure-guided discovery of submicromolar 1,2,4-triazole–Schiff-base inhibitors of glutathione reductase
Yazarlar (10)
Doç. Dr. Sevda MANAP Kafkas Üniversitesi, Türkiye
Arş. Gör. Hande Akar Gazi Üniversitesi, Türkiye
Doç. Dr. Hilal MEDETALİBEYOĞLU Kafkas Üniversitesi, Türkiye
Dr. Öğr. Üyesi Abdurrahman Atalay Avrasya Üniversitesi, Türkiye
Prof. Dr. Zehra Can Bayburt Üniversitesi, Türkiye
Arş. Gör. Yakup Kara Karadeniz Technical University, Türkiye
Prof. Dr. Muzaffer ALKAN Kafkas Üniversitesi, Türkiye
Doç. Dr. Murat BEYTUR Kafkas Üniversitesi, Türkiye
Haydar Yüksek Kafkas Üniversitesi, Türkiye
Ahmet Buğra Ortaakarsu
Gazi Üniversitesi, Türkiye
Gazi Üniversitesi, Türkiye
| Makale Türü | Özgün Makale (SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale) | ||
| Dergi Adı | International Journal of Biological Macromolecules (Q1) | ||
| Dergi ISSN | 0141-8130 Dergi Bilgileri (2026) | ||
| Makale Dili | İngilizce | Basım Tarihi | 01-2026 |
| Cilt / Sayı / Sayfa | 337 / 1 / – | DOI | 10.1016/j.ijbiomac.2025.149471 |
| Makale Linki | https://www.sciencedirect.com/science/article/pii/S0141813025100287 | ||
| UAK Araştırma Alanları |
Fen Bilimleri ve Matematik
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| Özet |
| Glutathione reductase (GR) plays a crucial role in maintaining cellular redox balance and is a promising target for ferroptosis-based cancer therapies. In this study, we report the design, synthesis, and comprehensive evaluation of a novel series of 1,2,4-triazole–Schiff base succinate derivatives (AUR-514–518) as potent GR inhibitors. In vitro Mannervik assays revealed vigorous submicromolar inhibitory activity, with AUR-517 emerging as the most effective (IC50 = 0.471 ± 0.032 μM), significantly surpassing quercetin (IC50 = 214.5 ± 18.5 μM). Antioxidant profiling revealed negligible radical scavenging activity; however, modest CUPRAC responses suggest a target-specific mechanism. To elucidate the molecular determinants of inhibition, we employed deep-learning–assisted protein–ligand affinity predictions, molecular dynamics simulations, MM/GBSA free-energy calculations, and dimensional … |
| Anahtar Kelimeler |
| 1,2,4-triazole–Schiff base | Antioxidant assays | Boltz-2 | Ferroptosis sensitization | Glutathione reductase | Molecular dynamics simulations |
Science Direct
Structure-guided discovery of submicromolar 1,2,4-triazole–Schiff-base inhibitors of glutathione reductase
BM Sürdürülebilir Kalkınma Amaçları
| Atıf Sayıları | |
| Scopus | 2 |
| Google Scholar | 3 |