A comprehensive investigation of Schiff bases and bis-α-aminophosphonates as potent agents against Alzheimer&#39;s disease by computer-aided drug discovery techniques and in vitro examinations

Ekinci, Emel; ÇİFTÇİ, HARUN; Adem, Şevki; GÜNDOĞDU AYTAÇ, ÖZLEM; Eyüpoğlu, Volkan

doi:10.1016/j.molstruc.2025.141734

A comprehensive investigation of Schiff bases and bis-α-aminophosphonates as potent agents against Alzheimer's disease by computer-aided drug discovery techniques and in vitro examinations

Yazarlar (5)
Emel Ekinci Çankırı Karatekin Üniversitesi, Türkiye
Prof. Dr. Harun ÇİFTÇİ Kurum Bilgileri Tıp Fakültesi Temel Tıp Bilimleri Tıbbi Biyokimya Özgeçmiş Sayfası İletişim Bilgileri: (376)218-9500 Kırşehir Ahi Evran Üniversitesi, Türkiye
Şevki Adem Çankırı Karatekin Üniversitesi, Türkiye
Doç. Dr. Özlem GÜNDOĞDU AYTAÇ Kurum Bilgileri Kaman Meslek Yüksekokulu Gıda İşleme Gıda Teknolojisi Pr. Özgeçmiş Sayfası İletişim Bilgileri: Kırşehir Ahi Evran Üniversitesi, Türkiye
Volkan Eyüpoğlu Çankırı Karatekin Üniversitesi, Türkiye

Devamını Göster

Özet

In this study, we designed and synthesized new Schiff bases (7–11) and bis-α-aminophosphonate derivatives (13–16) to examine their inhibitory properties against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes which are associated with Alzheimer's disease (AD). All newly synthesized compounds were characterized by FT-IR, ¹H, and ¹³C NMR and were tested were appraised for their inhibitory potential opposite to AChE and BChE enzymes, by determining their IC50 and Ki values. Bis-α-aminophosphonate derivatives showed significantly strong inhibitory affinity against AChE, whereas they had weak inhibitory activities against BChE. Schiff bases exhibited low inhibitory activity against both AChE and BChE. Among bis-α-aminophosphonates, compounds 14, 15, and 16 showed excellent inhibitory properties against AChE with an IC50 value of 6.48, 9.00, and 10.88 μM, respectively, with respect to positive control pyridostigmine bromide (IC50= 26.2 μM). Kinetic studies showed that the inhibition mechanism of 14, 15, and 16 against AChE is non-competitive. The physicochemical properties of compounds and their affinities towards the protein were investigated by quantum chemical calculations, molecular docking, and molecular dynamics simulation techniques. So, among the investigated compounds, compound 15 has been found as significantly higher binding affinity against AChE. This observation hints at the capacity of these compounds to potentially influence enzyme activity, indicating their potential relevance in the realm of treatment of Alzheimer's disease.

Anahtar Kelimeler

Makale Türü	Özgün Makale
Makale Alt Türü	SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale
Dergi Adı	Journal of Molecular Structure
Dergi ISSN	1872-8014 Wos Dergi Scopus Dergi
Dergi Tarandığı Indeksler	SCI-Expanded
Dergi Grubu	Q2
Makale Dili	Türkçe
Basım Tarihi	01-2025
Cilt No	1333
Sayı	1
Doi Numarası	10.1016/j.molstruc.2025.141734

BM Sürdürülebilir Kalkınma Amaçları

Atıf Sayıları
WoS	1
SCOPUS	1
Google Scholar	1

A comprehensive investigation of Schiff bases and bis-α-aminophosphonates as potent agents against Alzheimer's disease by computer-aided drug discovery techniques and in vitro examinations

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A comprehensive investigation of Schiff bases and bis-α-aminophosphonates as potent agents against Alzheimer's disease by computer-aided drug discovery techniques and in vitro examinations

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