| Yazarlar (6) |
Doç. Dr. Feyzi Sinan TOKALI
Kafkas Üniversitesi, Türkiye |
Halil Şenol
Bezm-İ Âlem Vakıf Üniversitesi, Türkiye |
|
Yeliz Demir
Ardahan Üniversitesi, Türkiye |
Dr. Öğr. Üyesi Orhan ULUÇAY
Kafkas Üniversitesi, Türkiye |
|
Mubashır Ameen
|
|
Zahıd Shafıq
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| Özet |
| Alzheimer's disease (AD) is a neurodegenerative disorder with a gradual increase in severity. The underlying cause of the disease is the dysfunction of cholinergic neurotransmission affecting mainly the activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Within the context of the present research, a new group of 3,5-disubstituted rhodanine derivatives containing tertiary amine groups has been prepared and their potency in the inhibition of AChE and BChE was assessed. Enzymatic assays demonstrated that compounds 6 and 11 exhibited exceptional inhibitory potency, with values of 13.61 nM and 12.70 nM against AChE, and 10.44 nM and 25.11 nM against BChE, respectively, surpassing the reference inhibitors tacrine (145.21 nM for AChE and 169.54 nM for BChE) and donepezil (67.41 nM for AChE and 62.44 nM for BChE). Cytotoxicity studies confirmed minimal toxicity in human umbilical vein endothelial cells (HUVEC) at concentrations several times higher than the effective inhibitory doses (IC = 79.13 µM for 6 and 69.14 µM for 11). The results from molecular docking and MM-GBSA calculations supported this presumption by foretelling strong binding affinities, where compound 11 was the one to show a free energy of -103.26 kcal mol for AChE and compound 6 -86.75 kcal mol for BChE. Moreover, the 250 ns molecular dynamics simulations gave a confirmation of the structural stability and the prolonged existence of the key interactions in the enzyme active sites during the entire time. The findings of this research emphasize compounds 6 and 11 as potential candidates for the creation of strong cholinesterase inhibitors for the treatment of Alzheimer's disease, thus encouraging additional studies. |
| Anahtar Kelimeler |
| Makale Türü |
Özgün Makale
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| Makale Alt Türü | SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale |
| Dergi Adı | RSC Advances |
| Dergi ISSN | 2046-2069 Wos Dergi Scopus Dergi |
| Dergi Tarandığı Indeksler | SCI-Expanded |
| Dergi Grubu | Q2 |
| Makale Dili | İngilizce |
| Basım Tarihi | 12-2025 |
| Cilt No | 15 |
| Sayı | 58 |
| Sayfalar | 50186 / 50205 |
| DOI Numarası | 10.1039/D5RA07416A |
| Makale Linki | https://doi.org/10.1039/d5ra07416a |
| Atıf Sayıları |
