| Yazarlar (6) |
Doç. Dr. Erbay KALAY
Kafkas Üniversitesi, Türkiye |
Halide Sedef Karaman
|
|
Osman Nuri Aslan
Atatürk Üniversitesi, Türkiye |
Doç. Dr. Feyzi Sinan TOKALI
Kafkas Üniversitesi, Türkiye |
|
Muhammet Karaman
Dokuz Eylül Üniversitesi, Türkiye |
Doç. Dr. Musa ERDOĞAN
Kafkas Üniversitesi, Türkiye |
| Özet |
| Glutathione reductase (GR) plays a pivotal role in cellular metabolism by maintaining redox balance and sulfhydryl homeostasis through the regeneration of reduced glutathione (GSH). In tumor cells, GR is overexpressed, supporting enhanced antioxidant defenses and neutralizing the detrimental effects of reactive oxygen species. In this study, a series of sulfonyl hydrazone analogs bearing phenolic Mannich base moieties were synthesized and characterized as potential GR inhibitors. The compounds exhibited inhibitory activity with IC values ranging from 198.1 to 3013 nM. In silico analyses revealed that 6a binds to the NADP binding site of the hGR enzyme and interacts with key residues involved in electron transfer, leading to reduced enzyme activity. Compound 6a, the most potent hGR enzyme inhibitor identified in this study, exhibited cytotoxic effects against MCF-7, A549, and HeLa cancer cell lines with EC values of ~1.52, ~17.5, and ~8.82 mM, respectively. Notably, compound 6a demonstrated only weak cytotoxicity at the millimolar level, particularly against the MCF-7 cell line. Given its strong inhibitory activity toward the hGR enzyme, enhancing the membrane permeability of compound 6a may improve its cellular uptake and potency, thereby supporting its potential as a promising anticancer drug candidate. |
| Anahtar Kelimeler |
| cell viability | enzyme inhibition | glutathione reductase | molecular docking | sulfonyl hydrazone |
| Makale Türü | Özgün Makale |
| Makale Alt Türü | SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale |
| Dergi Adı | Chemical Biology & Drug Design |
| Dergi ISSN | 1747-0277 Wos Dergi Scopus Dergi |
| Dergi Tarandığı Indeksler | SCI-Expanded |
| Dergi Grubu | Q2 |
| Makale Dili | İngilizce |
| Basım Tarihi | 11-2025 |
| Cilt No | 106 |
| Sayı | 5 |
| Doi Numarası | 10.1111/cbdd.70198 |
| Makale Linki | https://doi.org/10.1111/cbdd.70198 |
| Atıf Sayıları |
