| Yazarlar |
Doç. Dr. Turgay TUNÇ
Kırşehir Ahi Evran Üniversitesi, Türkiye |
Ahmet Bugra Ortaakarsu
|
|
Seda Muhsir Hatipoglu
|
|
Serdar Karaböcek
Türkiye |
|
Nevin Karaböcek
Türkiye |
|
Necmi Dege
Türkiye |
|
Nurcan Karacan
Türkiye |
|
Uğur Kazancı
|
| Özet |
| 2,6-bis(2-aminophenylthio)pyridine was synthesized and identified by x-ray diffraction method. Its new Schiffbases (H2L1, H2L2, L-3 and L-4) were synthesized and characterized by elemental analysis, FT-IR, LC-MS, H-1 NMR and C-13 NMR techniques. in vitro glutathione reductase activities of the compounds were tested on yeast and human glutathione reductase. L-4 enhanced both glutathione reductase activities, resulting in AC(50) values of 15.06 mu M and 15.89 mu M, respectively. H2L1, H2L2 and L-3 were found to be the inhibitors in the range of 50.09 - 55.23 mu M for yeast glutathione reductase, and in the range of 56.12-66.87 mu M for human glutathione reductase. According to molecular docking analysis at the xanthine binding site in human glutathione reductase (PDB: 1XAN), 2,6-bis(2-aminophenylthio)pyridine is predicted to have antimalarial property due to having a higher XP docking score than the malaria drug Chloroquine. Also, five binding pockets at the human glutathione reductase (PDB:1GRA) were identified using Sitemap analysis for Schiffbases which are non-competitive inhibitors. IFD-Docking scores were found to correlate with experimental IC50 value of H2L1, H2L2 and L-3. Based on the fact that Schiffbases have higher IFD docking scores at binding pocket-1 than at the active site, it can be predicted that Schiffbases prefer to bind to binding pocket-1 in the presence of natural substrate. The difference in glutathione reductase activities of Schiffbases was attributed to the fact that the conformation of the activator L-4-human GR complex was different from that of other inhibitor Schiffbases-human glutathione reductase complexes. ADMET calculations predicted that synthesized ligands obey the Lipinski Rule (rule of five) and Jorgensen Rule (rule of three). (C) 2022 Elsevier B.V. All rights reserved. |
| Anahtar Kelimeler |
| Glutathione reductase activator | Glutathione reductase inhibitor | Molecular docking | Schiff bases |
| Makale Türü | Özgün Makale |
| Makale Alt Türü | SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale |
| Dergi Adı | JOURNAL OF MOLECULAR STRUCTURE |
| Dergi ISSN | 0022-2860 |
| Dergi Tarandığı Indeksler | SCI-Expanded |
| Dergi Grubu | Q2 |
| Makale Dili | Türkçe |
| Basım Tarihi | 04-2022 |
| Cilt No | 1254 |
| Sayı | 1 |
| Doi Numarası | 10.1016/j.molstruc.2021.132299 |
| Makale Linki | http://dx.doi.org/10.1016/j.molstruc.2021.132299 |
| Atıf Sayıları | |
| WoS | 9 |
| SCOPUS | 7 |
| Google Scholar | 10 |
