| 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 |
| The rising incidence of type 2 diabetes mellitus (T2DM) and its related complications has created an urgent need for new therapeutic approaches. We herein describe the synthesis as well as biological investigation of a series of sixteen new phenolic Mannich base derivatives of thiazolidine-2,4-dione as α-glucosidase (α-Glu) and aldose reductase (ALR2) inhibitors, two crucial enzymes involved in T2DM and its complications. In vitro assays showed strong inhibitory activities, compound 12 (tetrahydroisoquinoline and α-methylcinnamyl substituted) exhibited the strongest inhibition of ALR2 (K: 0.024 µM); compound 10 (1-phenylpiperazine and α-methylcinnamyl substituted) displayed remarkable α-Glu inhibition (K: 0.370 µM). Computer-aided studies supported experimental observations and revealed key binding features like hydrogen bond, π-π stacking, and hydrophobic interactions, which were responsible for the exceptional binding capacity of the compound with the enzyme. Cytotoxicity assays performed on healthy cell lines (HUVEC and BEAS-B2) revealed that the tested compounds were non-toxic at inhibitory concentrations. ADME-T predictions indicated that compounds 10 and 12 satisfy key drug-likeness criteria, with favorable oral absorption and moderate solubility. These findings highlight the potential of compounds 10 and 12 as promising inhibitors for managing diabetes and its complications, providing a foundation for further optimization and therapeutic exploration. |
| Anahtar Kelimeler |
| Thiazolidin-2 | 4-dione | Mannich bases | Diabetes | alpha-Glucosidase | Aldose reductase |
| Makale Türü | Özgün Makale |
| Makale Alt Türü | SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale |
| Dergi Adı | Bioorganic & Medicinal Chemistry |
| Dergi ISSN | 0968-0896 Wos Dergi Scopus Dergi |
| Dergi Tarandığı Indeksler | SCI-Expanded |
| Dergi Grubu | Q1 |
| Makale Dili | İngilizce |
| Basım Tarihi | 06-2025 |
| Cilt No | 128 |
| Sayı | 118264 |
| Doi Numarası | 10.1016/j.bmc.2025.118264 |
| Makale Linki | https://doi.org/10.1016/j.bmc.2025.118264 |
| Atıf Sayıları | |
| WoS | 8 |
