Base-Catalyzed One-Pot Synthesis of Tetrahydrofuropyridinone Derivatives. Antioxidant and Molecular Docking Studies

A convenient one-pot synthesis of a novel series of 3-aryl-2-[4-(methylsulfanyl)benzoyl]-2,3,6,7-tetrahydrofuro[3,2-c]pyridin-4(5H)-ones 4a–4j by reacting piperidine-2,4-dione, 4-(methylsulfanyl)phenacyl bromide, and various aromatic aldehydes in the presence of a dual catalyst (triethylamine/pyridine) has been developed. The compounds were well characterized by spectroscopic techniques and evaluated for their antioxidant activity. Compounds 4a, 4c, and 4d exhibited excellent radical scavenging activity (IC50 = 656.2, 648.2, and 660.8 µM, respectively) compared to ascorbic acid (IC50 = 703.2 µM). Molecular docking studies were also performed against the enzyme myeloperoxidase to gain insights into the mechanistic basis for the antioxidant activity.