Development of phenolic Mannich bases as α-glucosidase and aldose reductase inhibitors: In vitro and in silico 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 | BIOORGANIC & MEDICINAL CHEMISTRY (Q1) | ||
| Dergi ISSN | 0968-0896 Wos Dergi Scopus Dergi | ||
| Dergi Tarandığı Indeksler | SCI-Expanded | ||
| Makale Dili | İngilizce | Basım Tarihi | 10-2025 |
| Cilt / Sayı / Sayfa | 128 / 118264 / – | DOI | 10.1016/j.bmc.2025.118264 |
| Makale Linki | https://doi.org/10.1016/j.bmc.2025.118264 | ||
| UAK Araştırma Alanları |
Organik Kimya
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| 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 |
BM Sürdürülebilir Kalkınma Amaçları
| Atıf Sayıları | |
| Web of Science | 35 |