| Yazarlar |
Gönül Yapar
Türkiye |
Doç. Dr. Hatice Esra DURAN
Kafkas Üniversitesi, Türkiye |
|
Nebih Lolak
Türkiye |
|
Süleyman Akocak
Türkiye |
|
Cüneyt Türkeş
Türkiye |
|
Mustafa Durgun
Türkiye |
|
Mesut Işık
Bilecik Şeyh Edebali Üniversitesi, Türkiye |
|
Şükrü Beydemir
Anadolu Üniversitesi, Türkiye |
| Özet |
| Aldose reductase (ALR2), one of the metabolically important enzymes, catalyzes the formation of sorbitol from glucose in the polyol pathway. ALR2 inhibition is required to prevent diabetic complications. In the present study, the novel bis-hydrazone compounds bearing isovanillin moiety (GY1-12) were synthesized, and various chromatographic methods were applied to purify the ALR2 enzyme. Afterward, the inhibitory effect of the synthesized compounds on the ALR2 was screened in vitro. All the novel bis-hydrazones demonstrated activity in nanomolar levels as AR inhibitors with IC and K values in the range of 12.55-35.04 nM, and 13.38-88.21 nM, respectively. Compounds GY-11, GY-7, and GY-5 against ALR2 were identified as the highly potent inhibitors, respectively, and were superior to the standard drug, epalrestat. Moreover, a comprehensive ligand-receptor interactions prediction was performed using ADME-Tox, Glide XP, and MM-GBSA modules of Schrödinger Small-Molecule Drug Discovery Suite to elucidate the novel bis-hydrazone derivatives, potential binding modes versus the ALR2. As a result, these compounds with ALR2 inhibitory effects may be potential alternative agents that can be used to treat or prevent diabetic complications. |
| Anahtar Kelimeler |
| Aldose reductase | Bis-hydrazones | Epalrestat | In silico study | ADME-Tox |
| Makale Türü | Özgün Makale |
| Makale Alt Türü | SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale |
| Dergi Adı | BIOORGANIC CHEMISTRY |
| Dergi ISSN | 0045-2068 |
| Dergi Tarandığı Indeksler | SCI-Expanded |
| Dergi Grubu | Q1 |
| Makale Dili | Türkçe |
| Basım Tarihi | 12-2021 |
| Cilt No | 117 |
| Sayfalar | 105473 / 0 |
| Doi Numarası | 10.1016/j.bioorg.2021.105473 |
| Makale Linki | http://dx.doi.org/10.1016/j.bioorg.2021.105473 |
| Atıf Sayıları | |
| WoS | 51 |
| Google Scholar | 58 |
