Barbiturate-sulfonate hybrids as potent cholinesterase inhibitors: design, synthesis and molecular modeling studies

• Published in: Future medicinal chemistry Vol. 16; no. 16; p. 1615
• Main Authors: Kassem, Asmaa F, Omar, Mohamed A, Temirak, Ahmed, El-Shiekh, Riham A, Srour, Aladdin M
• Format: Journal Article
• Language: English
• Published: England 17.08.2024
• Subjects: Acetylcholinesterase - metabolism; Animals; Barbiturates - chemical synthesis; Barbiturates - chemistry; Barbiturates - pharmacology; Butyrylcholinesterase - metabolism; Cholinesterase Inhibitors - chemical synthesis; Cholinesterase Inhibitors - chemistry; Cholinesterase Inhibitors - pharmacology; Drug Design; Humans; Models, Molecular; Molecular Docking Simulation; Molecular Structure; Structure-Activity Relationship; Sulfonic Acids - antagonists & inhibitors; Sulfonic Acids - chemistry; Sulfonic Acids - pharmacology; antioxidant; barbiturate-sulfonate; cholinesterase; molecular modeling; Alzheimer's
• ISSN: 1756-8927
• DOI: 10.1080/17568919.2024.2366158

Design and synthesis of a series of 5-benzylidene(thio)barbiturates . Evaluation of the inhibitory activity of the new chemical entities on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using Donepezil as the standard reference. Compound emerged as the most potent AChE inhibitor (IC  = 9.12 μM), while compound exhibited the highest inhibitory activity against BChE (IC  = 19.43 μM). Toxicological bioassays confirmed the absence of cytotoxicity for the most potent compounds at the tested doses. Molecular docking analysis demonstrated that the tested derivatives effectively bind to the active sites of both enzymes. Overall, this study sheds light on the potential of barbiturate-sulfonate conjugates as promising drug candidates.