Synthesis of novel thiosemicarbazone derivatives and investigation of their dual <scp>AChE</scp> and <scp>MAO‐B</scp> inhibitor effects

Uytun, A.; Osmaniye, Derya; Sağlık, Begüm Nurpelin; Levent, Serkan; Özkay, Yusuf; Kaplancıklı, Zafer Asım

doi:10.1002/jmr.2990

Cited by 3 publications

(1 citation statement)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…AChE inhibitors are the main class of drugs used to treat AD. Four out of the five drugs (tacrine, donepezil, galantamine, rivastigmine) approved by the Food and Drug Administration and available for the treatment of AD are AChE inhibitors (Marucci et al, 2021; Saǧllk, 2022; Uytun et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

Synthesis of new N‐(5,6‐methylenedioxybenzothiazole‐2‐yl)‐2‐[(substituted)thio/piperazine]acetamide/propanamide derivatives and evaluation of their AChE, BChE, and BACE‐1 inhibitory activities

Tutuş,

Kaya,

Baz

et al. 2024

Drug Development Research

View full text Add to dashboard Cite

In this study, the synthesis of N‐(5,6‐methylenedioxybenzothiazole‐2‐yl)‐2‐[(substituted)thio/piperazine]acetamide/propanamide derivatives (3a‐3k) and to investigate their acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and β‐secretase 1 (BACE‐1) inhibition activity were aimed. Mass, 1H NMR, and 13C NMR spectra were utilized to determine the structure of the synthesized compounds. Compounds 3b, 3c, 3f, and 3j showed AChE inhibitory activity which compound 3c (IC50 = 0.030 ± 0.001 µM) showed AChE inhibitory activity as high as the reference drug donepezil (IC50 = 0.0201 ± 0.0010 µM). Conversely, none of the compounds showed BChE activity. Compounds 3c and 3j showed the highest BACE‐1 inhibitory activity and IC50 value was found as 0.119 ± 0.004 µM for compound 3j whereas IC50 value was 0.110 ± 0.005 µM for donepezil, which is one of the reference substance. Molecular docking studies have been carried out using the data retrieved from the server of the Protein Data Bank (PDBID: 4EY7 and 2ZJM). Using in silico approach behavior active compounds (3c and 3j) and their binding modes clarified.

show abstract

Section: Introductionmentioning

confidence: 99%

Synthesis of new N‐(5,6‐methylenedioxybenzothiazole‐2‐yl)‐2‐[(substituted)thio/piperazine]acetamide/propanamide derivatives and evaluation of their AChE, BChE, and BACE‐1 inhibitory activities

Tutuş,

Kaya,

Baz

et al. 2024

Drug Development Research

View full text Add to dashboard Cite

show abstract

Design, synthesis, molecular modeling, in vitro evaluation of novel piperidine‐containing hydrazone derivatives as cholinesterase inhibitors

Tok,

Baltaş,

Abas

et al. 2024

Drug Development Research

View full text Add to dashboard Cite

In an effort to develop new and effective therapeutic agents for Alzheimer's disease, a series of hydrazone derivatives bearing piperidine rings have been designed and synthesized. The chemical structures of the compounds were characterized by various spectroscopic techniques. In vitro antioxidant and cholinesterase activities of the compounds were evaluated. Among the compounds, N12 exhibited the most antioxidant activity in all methods (CUPRAC, FRAP, DPPH, ABTS). In vitro acetylcholinesterase (AChE) activity results of the compounds showed good IC50 values between 14.124 ± 0.084 and 49.680 ± 0.110 µM were obtained (IC50 = 38.842 ± 0.053 µM for Donepezil). Among the compounds, N7 and N6 are much more effective derivatives than the standard compound donepezil with IC50 values of 14.124 ± 0.084 and 17.968 ± 0.072 µM, respectively. In vitro, butyrylcholinesterase (BChE) inhibition values of the compounds were between 13.505 ± 0.025 and 52.230 ± 0.027 μm. Among the compounds, N6 has the highest BChE inhibition with an IC50 value of 13.505 μm in the series. The cytotoxicity and AChE inhibitory activity of the compounds on SH‐SY5Y cell lines were also evaluated. Kinetic studies were also performed to determine the behavior of the compounds as competitive or noncompetitive inhibitors. The binding modes of N6, which was determined to be highly effective according to in vitro analyses, with AChE and BChE were investigated using molecular docking studies, and the stability of the complexes was determined by molecular dynamics simulations. These findings indicated that AChE and BChE enzymes maintained their overall structural stability and compactness during interactions with compound N6.

show abstract

A novel series of thiosemicarbazone hybrid scaffolds: Design, synthesis, DFT studies, metabolic enzyme inhibition properties, and molecular docking calculations

Yakan

Muğlu

Türkeş

et al. 2023

Journal of Molecular Structure

View full text Add to dashboard Cite

Synthesis of novel thiosemicarbazone derivatives and investigation of their dual AChE and MAO‐B inhibitor effects

Cited by 3 publications

References 31 publications

Synthesis of new N‐(5,6‐methylenedioxybenzothiazole‐2‐yl)‐2‐[(substituted)thio/piperazine]acetamide/propanamide derivatives and evaluation of their AChE, BChE, and BACE‐1 inhibitory activities

Synthesis of new N‐(5,6‐methylenedioxybenzothiazole‐2‐yl)‐2‐[(substituted)thio/piperazine]acetamide/propanamide derivatives and evaluation of their AChE, BChE, and BACE‐1 inhibitory activities

Design, synthesis, molecular modeling, in vitro evaluation of novel piperidine‐containing hydrazone derivatives as cholinesterase inhibitors

A novel series of thiosemicarbazone hybrid scaffolds: Design, synthesis, DFT studies, metabolic enzyme inhibition properties, and molecular docking calculations

Contact Info

Product

Resources

About