Quinazolin‐4(3H)‐One‐Based New Glitazones as Dual Inhibitors of α‐Glucosidase and Aldose Reductase: Comprehensive Approaches for Managing Diabetes Mellitus and Its Complications
Yazarlar (5)
Doç. Dr. Feyzi Sinan TOKALI Kafkas Üniversitesi, Türkiye
Prof. Dr. Yeliz Demir Ardahan Üniversitesi, Türkiye
Arş. Gör. Şeyma Ateşoğlu Bezm-İ Âlem Vakıf Üniversitesi, Türkiye
Pelin Tokalı
Doç. Dr. Halil Şenol Bezm-İ Âlem Vakıf Üniversitesi, Türkiye
| Makale Türü | Özgün Makale (SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale) | ||
| Dergi Adı | ARCHIV DER PHARMAZIE (Q2) | ||
| Dergi ISSN | 0365-6233 Wos Dergi Scopus Dergi | ||
| Dergi Tarandığı Indeksler | SCI-Expanded | ||
| Makale Dili | İngilizce | Basım Tarihi | 06-2025 |
| Cilt / Sayı / Sayfa | 358 / 6 / – | DOI | 10.1002/ardp.70033 |
| Makale Linki | https://doi.org/10.1002/ardp.70033 | ||
| UAK Araştırma Alanları |
Organik Kimya
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| 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 |
BM Sürdürülebilir Kalkınma Amaçları
| Atıf Sayıları | |
| Web of Science | 25 |