img
img
img

Akademisyenler > Orhan ULUÇAY > Yayın Detayı

New Mannich-type arylidenerhodanines as potent inhibitors of AChE and BChE: synthesis, biological evaluation, cytotoxicity and molecular modeling     
Yazarlar (6)
Doç. Dr. Feyzi Sinan TOKALI 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 Dr. Öğr. Üyesi Orhan ULUÇAY
Kafkas Üniversitesi, Türkiye
Mubashır Ameen
Zahıd Shafıg
Devamını Göster
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 Ki 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 (IC50 = 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−1 for AChE and compound 6 −86.75 kcal mol−1 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 Açık Erişim Özgün Makale
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
BM Sürdürülebilir Kalkınma Amaçları
Atıf Sayıları
New Mannich-type arylidenerhodanines as potent inhibitors of AChE and BChE: synthesis, biological evaluation, cytotoxicity and molecular modeling

Paylaş