Synthesis, Molecular Simulation, DFT, and Kinetic Study of Imidazotriazole-Based Thiazolidinone as Dual Inhibitor of Acetylcholinesterase and Butyrylcholinesterase Enzymes DOI Creative Commons
Manal M. Khowdiary, Shoaib Khan,

Tayyiaba Iqbal

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(3), P. 415 - 415

Published: March 15, 2025

Background: Alzheimer’s disease is a complex and multifactorial brain disorder characterized by gradual memory impairment, cognitive disturbance, severe dementia, and, ultimately, its progression leads to patient death. This research work presents the design, synthesis, characterization of novel imidazotriazole-based thiazolidinone derivatives (1–14), displaying promising anti-Alzheimer’s activity. Methods: These were synthesized using 1H-imidazole-2-thiol as starting reagent. Structural was accomplished 13C-NMR 1H-NMR, while molecular weight confirmed HREI-MS. compounds investigated for their potential under an in vitro analysis. Results: showed significant moderate biological against AChE BChE comparison donepezil (IC50 = 8.50 µM 8.90 BuChE), used reference drug. Among these compounds, analog 10 with IC50 values 6.70 7.10 BuChE emerged lead compound series efficacy targeted enzymes. Molecular docking revealed interactive nature active ligands target also assessed dynamic conditions examine structural deviation conformational changes protein structure. DFT calculations provided relative stability reactivity compounds. An ADMET analysis that have no toxicological profile. Conclusions: study paves way further development optimization selective inhibitors potent agents.

Language: Английский

Synthesis, Molecular Simulation, DFT, and Kinetic Study of Imidazotriazole-Based Thiazolidinone as Dual Inhibitor of Acetylcholinesterase and Butyrylcholinesterase Enzymes DOI Creative Commons
Manal M. Khowdiary, Shoaib Khan,

Tayyiaba Iqbal

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(3), P. 415 - 415

Published: March 15, 2025

Background: Alzheimer’s disease is a complex and multifactorial brain disorder characterized by gradual memory impairment, cognitive disturbance, severe dementia, and, ultimately, its progression leads to patient death. This research work presents the design, synthesis, characterization of novel imidazotriazole-based thiazolidinone derivatives (1–14), displaying promising anti-Alzheimer’s activity. Methods: These were synthesized using 1H-imidazole-2-thiol as starting reagent. Structural was accomplished 13C-NMR 1H-NMR, while molecular weight confirmed HREI-MS. compounds investigated for their potential under an in vitro analysis. Results: showed significant moderate biological against AChE BChE comparison donepezil (IC50 = 8.50 µM 8.90 BuChE), used reference drug. Among these compounds, analog 10 with IC50 values 6.70 7.10 BuChE emerged lead compound series efficacy targeted enzymes. Molecular docking revealed interactive nature active ligands target also assessed dynamic conditions examine structural deviation conformational changes protein structure. DFT calculations provided relative stability reactivity compounds. An ADMET analysis that have no toxicological profile. Conclusions: study paves way further development optimization selective inhibitors potent agents.

Language: Английский

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