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

Yazarlar (5)

Emel Ekinci
Çankırı Karatekin Üniversitesi, Türkiye

Prof. Dr. Harun ÇİFTÇİ Kırşehir Ahi Evran Üniversitesi, Türkiye

Şevki Adem
Çankırı Karatekin Üniversitesi, Türkiye

Doç. Dr. Özlem GÜNDOĞDU AYTAÇ Kırşehir Ahi Evran Üniversitesi, Türkiye

Volkan Eyüpoğlu
Çankırı Karatekin Üniversitesi, Türkiye

Makale Türü	Özgün Makale (SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale)
Dergi Adı	Journal of Molecular Structure (Q2)
Dergi ISSN	0022-2860 Wos Dergi Scopus Dergi
Dergi Tarandığı Indeksler	SCI-Expanded
Makale Dili	İngilizce	Basım Tarihi	06-2025
Cilt / Sayı / Sayfa	1333 / 1 / –	DOI	10.1016/j.molstruc.2025.141734
Makale Linki	https://doi.org/10.1016/j.molstruc.2025.141734

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

Science Direct

BM Sürdürülebilir Kalkınma Amaçları

Atıf Sayıları
WoS	3
SCOPUS	3
Google Scholar	3

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

Dergi Adı	Journal of Molecular Structure
Yayıncı	Elsevier B.V.
Açık Erişim	Hayır
ISSN	0022-2860
E-ISSN	1872-8014
CiteScore	8,0
SJR	0,628
SNIP	0,999

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

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