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Design, synthesis, molecular modeling, in vitro evaluation of novel piperidine-containing hydrazone derivatives as cholinesterase inhibitors.
Tok, Fatih; Baltas, Nimet; Abas, Burçin Irem; Tatar Yilmaz, Gizem; Kaya, Süleyman; Koçyigit-Kaymakçioglu, Bedia; Çevik, Özge.
Afiliación
  • Tok F; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Marmara University, Istanbul, Türkiye.
  • Baltas N; Department of Chemistry, Faculty of Arts and Sciences, Recep Tayyip Erdogan University, Rize, Türkiye.
  • Abas BI; Department of Biochemistry, School of Medicine, Aydin Adnan Menderes University, Aydin, Türkiye.
  • Tatar Yilmaz G; Department of Biostatistics and Medical Informatics, Faculty of Medicine, Karadeniz Technical University, Trabzon, Türkiye.
  • Kaya S; Department of Biostatistics and Medical Informatics, Faculty of Medicine, Karadeniz Technical University, Trabzon, Türkiye.
  • Koçyigit-Kaymakçioglu B; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Biruni University, Istanbul, Türkiye.
  • Çevik Ö; Department of Biochemistry, School of Medicine, Aydin Adnan Menderes University, Aydin, Türkiye.
Drug Dev Res ; 85(5): e22240, 2024 Aug.
Article en En | MEDLINE | ID: mdl-39105636
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Piperidinas / Acetilcolinesterasa / Butirilcolinesterasa / Diseño de Fármacos / Inhibidores de la Colinesterasa / Simulación del Acoplamiento Molecular / Hidrazonas Límite: Humans Idioma: En Revista: Drug Dev Res Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Piperidinas / Acetilcolinesterasa / Butirilcolinesterasa / Diseño de Fármacos / Inhibidores de la Colinesterasa / Simulación del Acoplamiento Molecular / Hidrazonas Límite: Humans Idioma: En Revista: Drug Dev Res Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos