Synthesis, biological evaluation, and in silico study of novel library sulfonates containing quinazolin-4(3H)-one derivatives as potential aldose reductase inhibitors
Yazarlar (7)
Doç. Dr. Feyzi Sinan TOKALI
Kafkas Üniversitesi, Türkiye
Yeliz Demir
Türkiye
İbrahim Hakkı Demircioğlu
Türkiye
Cüneyt Türkeş
Türkiye
Doç. Dr. Erbay KALAY
Kafkas Üniversitesi, Türkiye
Kıvılcım Şendil
Kafkas Üniversitesi, Türkiye
Şükrü Beydemir
Türkiye
| Makale Türü | Özgün Makale (SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale) | ||
| Dergi Adı | DRUG DEVELOPMENT RESEARCH (Q2) | ||
| Dergi ISSN | 0272-4391 Wos Dergi Scopus Dergi | ||
| Dergi Tarandığı Indeksler | SCI-Expanded | ||
| Makale Dili | İngilizce | Basım Tarihi | 05-2022 |
| Cilt / Sayı / Sayfa | 83 / 3 / 586–604 | DOI | 10.1002/ddr.21887 |
| Makale Linki | http://dx.doi.org/10.1002/ddr.21887 | ||
| Özet |
| A series of novel sulfonates containing quinazolin-4(3H)-one ring derivatives was designed to inhibit aldose reductase (ALR2, EC 1.1.1.21). Novel quinazolinone derivatives (1-21) were synthesized from the reaction of sulfonated aldehydes with 3-amino-2-alkylquinazolin-4(3H)-ones in glacial acetic acid with good yields (85%-94%). The structures of the novel molecules were characterized using IR, H-NMR, C-NMR, and HRMS. All the novel quinazolinones (1-21) demonstrated nanomolar levels of inhibitory activity against ALR2 (K s are in the range of 101.50-2066.00 nM). Besides, 4-[(2-isopropyl-4-oxoquinazolin-3[4H]-ylimino)methyl]phenyl benzenesulfonate (15) showed higher inhibitor activity inhibited ALR2 up to 7.7-fold compared to epalrestat, a standard inhibitor. Binding interactions between ALR2 and quinazolinones have been investigated using Schrödinger Small-Molecule Drug Discovery Suite 2021-1, reported possible inhibitor-ALR2 interactions. Both in vitro and in silico study results suggest that these quinazolin-4(3H)-one ring derivatives (1-21) require further molecular modification to improve their drug nominee potency as an ALR2 inhibitor. |
| Anahtar Kelimeler |
| ADME-Tox | aldose reductase | epalrestat | in silico study | molecular docking | quinazolinones |
BM Sürdürülebilir Kalkınma Amaçları
| Atıf Sayıları | |
| WoS | 90 |