Synthesis, Antioxidant and Some Enzyme Inhibition Activities of New Sulfonyl Hydrazones and their Molecular Docking Simulations

Aktar, Bedriye Seda Kurşun; Sıcak, Yusuf; Tatar, Gizem; Oruç‐Emre, Emine Elçin

doi:10.1007/s11094-022-02674-3

Cited by 5 publications

(2 citation statements)

References 33 publications

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“…The choice of aforementioned crystallographic structures followed previous investigations of Alov et al [ 46 ], who, aiming at multi-target hit compounds for neurodegenerative disease drug development, performed molecular docking in AChE (PDB ID 4EY7). Aktar et al [ 75 ] have investigated the enzyme inhibition activities of new sulfonyl hydrazones performing molecular docking simulations in BChE (PDB ID 6QAA).…”

Section: Methodsmentioning

confidence: 99%

Design, Synthesis, In Silico Studies and In Vitro Evaluation of New Indole- and/or Donepezil-like Hybrids as Multitarget-Directed Agents for Alzheimer’s Disease

Angelova,

Georgiev,

Pencheva

et al. 2023

Pharmaceuticals

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Alzheimer’s disease (AD) is considered a complex neurodegenerative condition which warrants the development of multitargeted drugs to tackle the key pathogenetic mechanisms of the disease. In this study, two novel series of melatonin- and donepezil-based hybrid molecules with hydrazone (3a–r) or sulfonyl hydrazone (5a–l) fragments were designed, synthesized, and evaluated as multifunctional ligands against AD-related neurodegenerative mechanisms. Two lead compounds (3c and 3d) exhibited a well-balanced multifunctional profile, demonstrating intriguing acetylcholinesterase (AChE) inhibition, promising antioxidant activity assessed by DPPH, ABTS, and FRAP methods, as well as the inhibition of lipid peroxidation in the linoleic acid system. Compound 3n, possessing two indole scaffolds, showed the highest activity against butyrylcholinesterase (BChE) and a high selectivity index (SI = 47.34), as well as a pronounced protective effect in H2O2-induced oxidative stress in SH-SY5Y cells. Moreover, compounds 3c, 3d, and 3n showed low neurotoxicity against malignant neuroblastoma cell lines of human (SH-SY5Y) and murine (Neuro-2a) origin, as well as normal murine fibroblast cells (CCL-1) that indicate the in vitro biocompatibility of the experimental compounds. Furthermore, compounds 3c, 3d, and 3n were capable of penetrating the blood–brain barrier (BBB) in the experimental PAMPA-BBB study. The molecular docking showed that compound 3c could act as a ligand to both MT1 and MT2 receptors, as well as to AchE and BchE enzymes. Taken together, those results outline compounds 3c, 3d, and 3n as promising prototypes in the search of innovative compounds for the treatment of AD-associated neurodegeneration with oxidative stress. This study demonstrates that hydrazone derivatives with melatonin and donepezil are appropriate for further development of new AChE/BChE inhibitory agents.

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Section: Methodsmentioning

confidence: 99%

Design, Synthesis, In Silico Studies and In Vitro Evaluation of New Indole- and/or Donepezil-like Hybrids as Multitarget-Directed Agents for Alzheimer’s Disease

Angelova,

Georgiev,

Pencheva

et al. 2023

Pharmaceuticals

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“…Therefore, organic compounds with the potential to inhibit the AChE enzyme are becoming more and more important in the treatment of neurodegenerative disease. [30,31] Considering the importance of sulfonyl hydrazone derivaties, it is worthwhile to design and synthesis a novel sulfonyl hydrazone derivatives, which was expected to possess good antioxidant activity along with acetylcholinesterase inhibitor potentials. We here in designed, synthesized novel aryl sulfonyl hydrazone derivatives and investigated their acetylcholinesterase (AChE) inhibition properties and antioxidant activities in vitro.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Arylsulfonyl Hydrazone Derivatives: Antioxidant Activity, Acetylcholinesterase Inhibition Properties, and Molecular Docking Study

Demirci,

Kalay,

Kara

et al. 2023

ChemistrySelect

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In this current paper, fifteen novel sulfonyl hydrazone derivatives have been successfully synthesized and evaluated for antioxidant activity as well as their effects on inhibitory activity toward acetylcholinesterase (AChE). By using 1H NMR, 13C NMR, FT‐IR, and high‐resolution mass spectrometry methods, the full characterization data of the novel compounds were obtained. The synthesized compounds capacity to inhibition glucosidase and exhibit antioxidant activity were tested in vitro. It was determined that compounds (E)‐4‐((2‐((4‐chlorophenyl)sulfonyl)hydrazone)methyl)‐2‐methoxyphenylfuran‐2‐carboxylate (21), (E)‐2‐methoxy‐4‐((2‐(phenylsulfonyl)hydrazone)methyl)phenylfuran‐2‐carboxylate (17) and (E)‐4‐((2‐((4‐bromophenyl)sulfonyl)hydrazone)methyl)‐2‐methoxyphenylfuran‐2‐carboxylate (25) showed good antioxidant activity. Upon examining the acetylcholinesterase inhibitory activity, it was determined that compounds (E)‐2‐methoxy‐4‐((2‐((4‐methoxyphenyl)sulfonyl) hydrazone)methyl)phenylacetate (27) (10.39 μM), (E)‐4‐((2‐((4‐chloro phenyl)sulfonyl) hydrazone)methyl)‐2‐methoxyphenylfuran‐2‐carboxylate (21) (10.81 μM), (E)‐4‐((2‐((4‐chloro phenyl)sulfonyl)hydrazone)methyl)‐2‐methoxyphenyl thiophene‐2‐carboxylate (22) (12.92 μM) and (E)‐2‐methoxy‐4‐((2‐(phenylsulfonyl)hydrazone)methyl)phenylfuran‐2‐carboxylate (17) (12.93 μM) showed potent inhibitory effects. Molecular docking simulations were used to investigate the interactions of novel sulfonyl hydrazone derivatives with human acetylcholinesterase protein. The ligands exhibited strong binding to the receptor protein with potent inhibition.

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Chiral thioureas containing naphthalene moiety as selective butyrylcholinesterase inhibitors: Design, synthesis, cholinesterase inhibition activity and molecular docking studies

Karaküçük-İyidoğan,

Sıcak,

Uysal

et al. 2025

Journal of Molecular Structure

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Synthesis, Antioxidant and Some Enzyme Inhibition Activities of New Sulfonyl Hydrazones and their Molecular Docking Simulations

Cited by 5 publications

References 33 publications

Design, Synthesis, In Silico Studies and In Vitro Evaluation of New Indole- and/or Donepezil-like Hybrids as Multitarget-Directed Agents for Alzheimer’s Disease

Design, Synthesis, In Silico Studies and In Vitro Evaluation of New Indole- and/or Donepezil-like Hybrids as Multitarget-Directed Agents for Alzheimer’s Disease

Synthesis of Arylsulfonyl Hydrazone Derivatives: Antioxidant Activity, Acetylcholinesterase Inhibition Properties, and Molecular Docking Study

Chiral thioureas containing naphthalene moiety as selective butyrylcholinesterase inhibitors: Design, synthesis, cholinesterase inhibition activity and molecular docking studies

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