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

Autor: Kassem AF; Department of Chemistry, College of Science & Humanities in Al-Kharj, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.; Chemistry of Natural & Microbial Products Department, Pharmaceutical & Drug Industries Research Institute, National Research Centre, Dokki, Giza 12622, Egypt., Omar MA; Chemistry of Natural & Microbial Products Department, Pharmaceutical & Drug Industries Research Institute, National Research Centre, Dokki, Giza 12622, Egypt., Temirak A; Chemistry of Natural & Microbial Products Department, Pharmaceutical & Drug Industries Research Institute, National Research Centre, Dokki, Giza 12622, Egypt., El-Shiekh RA; Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr el Aini St., 11562, Cairo, Egypt., Srour AM; Department of Therapeutic Chemistry, Pharmaceutical & Drug Industries Research Institute, National Research Centre, Dokki, Giza 12622, Egypt.
Jazyk: angličtina
Zdroj: Future medicinal chemistry [Future Med Chem] 2024 Aug 17; Vol. 16 (16), pp. 1615-1631. Date of Electronic Publication: 2024 Jul 16.
DOI: 10.1080/17568919.2024.2366158
Abstrakt: Aim: Design and synthesis of a series of 5-benzylidene(thio)barbiturates 3a-r . Methodology: Evaluation of the inhibitory activity of the new chemical entities on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using Donepezil as the standard reference. Results & Conclusion: Compound 3r emerged as the most potent AChE inhibitor (IC 50  = 9.12 μM), while compound 3q exhibited the highest inhibitory activity against BChE (IC 50  = 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.
Databáze: MEDLINE
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