| Yazarlar (5) |
Doç. Dr. Feyzi Sinan TOKALI
Kafkas Üniversitesi, Türkiye |
Yeliz Demir
Ardahan Üniversitesi, Türkiye |
|
Şeyma Ateşoğlu
Bezm-İ Âlem Vakıf Üniversitesi, Türkiye |
|
Pelin Tokalı
|
|
Halil Şenol
Bezm-İ Âlem Vakıf Üniversitesi, Türkiye |
| Özet |
| A series of novel glitazones containing thiazolidine-2,4-dione and quinazolin-4(3H)-one moieties were synthesized to explore their potential as dual inhibitors of aldose reductase (ALR2) and α-glucosidase (α-Glu), two key enzymes involved in diabetes and its complications. In vitro assays revealed that compounds 8 (cyclohexyl substituted), 9 (phenethyl substituted), and 11 (phenyl substituted) exhibited potent inhibitory effects on both enzymes, with 11 being the most active, showing an ALR2 inhibition (K = 0.106 µM) approximately nine times more effective than the standard epalrestat (EPR) (K = 0.967 µM) and α-Glu inhibition (K = 0.648 µM) about six times stronger than acarbose (ACR) (K = 0.3.775 µM). Molecular docking and molecular dynamics simulations showed that compound 11 formed strong interactions with residues Trp-20, Gln-183, and Asp-43 for ALR2 and residues Arg-200, Arg-400, and Glu-271 for Phe-297. Cytotoxicity assays performed on healthy cell lines (HUVEC and BEAS-B2) revealed that the tested compounds were nontoxic at inhibitory concentrations. These findings highlight the potential of compound 11 as a promising dual inhibitor for managing diabetes and its complications, providing a foundation for further optimization and therapeutic exploration. |
| Anahtar Kelimeler |
| aldose reductase | diabetes | glitazones | quinazolin-4(3 |
| Makale Türü | Özgün Makale |
| Makale Alt Türü | SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale |
| Dergi Adı | Archiv der Pharmazie |
| Dergi ISSN | 0365-6233 Wos Dergi Scopus Dergi |
| Dergi Tarandığı Indeksler | SCI-Expanded |
| Dergi Grubu | Q2 |
| Makale Dili | İngilizce |
| Basım Tarihi | 06-2025 |
| Cilt No | 358 |
| Sayı | 6 |
| Doi Numarası | 10.1002/ardp.70033 |
| Makale Linki | https://doi.org/10.1002/ardp.70033 |
| Atıf Sayıları | |
| WoS | 6 |
