| Yazarlar (5) |
Doç. Dr. Feyzi Sinan TOKALI
Kafkas Üniversitesi, Türkiye |
Yeliz Demir
Ardahan Üniversitesi, Türkiye |
|
Cüneyt Türkeş
Erzincan Binali Yıldırım Üniversitesi, Türkiye |
|
Büşra Dincer
Türkiye |
|
Şükrü Beydemir
Anadolu Üniversitesi, Türkiye |
| Özet |
| Aldose reductase (AR) is a crucial enzyme of the polyol pathway through which glucose is metabolized under conditions of hyperglycemia related to diabetes. A series of novel acetic acid derivatives containing quinazolin-4(3H)-one ring (1-22) was synthesized and tested for in vitro AR inhibitory effect. All the target compounds exhibited nanomolar activity against the target enzyme, and all compounds displayed higher activity as compared to the reference drug epalrestat. Among them, Compound 19, named 2-(4-[(2-[(4-methylpiperazin-1-yl)methyl]-4-oxoquinazolin-3(4H)-ylimino)methyl]phenoxy)acetic acid, displayed the strongest inhibitory effect with a K value of 61.20 ± 10.18 nM. Additionally, these compounds were investigated for activity against L929, nontumoral fibroblast cells, and MCF-7, breast cancer cells using the MTT assay. Compounds 16 and 19 showed lower toxicity against the normal L929 cells. The synthesized compounds' (1-22) absorption, distribution, metabolism, and excretion properties were also evaluated. Molecular docking simulations were used to look into the possible binding mechanisms of these inhibitors against AR. |
| Anahtar Kelimeler |
| ADME | aldose reductase | molecular docking | synthesis | quinazolines |
| Makale Türü | Özgün Makale |
| Makale Alt Türü | SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale |
| Dergi Adı | Drug Development Research |
| Dergi ISSN | 0272-4391 Wos Dergi Scopus Dergi |
| Dergi Tarandığı Indeksler | SCI-Expanded |
| Dergi Grubu | Q2 |
| Makale Dili | İngilizce |
| Basım Tarihi | 04-2023 |
| Cilt No | 84 |
| Sayı | 2 |
| Sayfalar | 275 / 295 |
| Doi Numarası | 10.1002/ddr.22031 |
| Makale Linki | http://dx.doi.org/10.1002/ddr.22031 |
| Atıf Sayıları | |
| WoS | 42 |
