ANTICHOLINESTERASE AND ANTIRADICAL ACTIVITIES OF FUNCTIONALLY SUBSTITUTED 2(5H)-FURANONES AND THEIR DERIVATIVES

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Biochemistry

Background:

• Cholinesterase inhibitors are crucial for treating neurodegenerative diseases.
• Antioxidants play a vital role in combating oxidative stress.
• 2(5H)-furanones are a versatile scaffold for drug discovery.

Purpose of the Study:

• To synthesize and evaluate novel 2(5H)-furanone derivatives.
• To assess their anticholinesterase activity against human erythrocyte acetylcholinesterase (AChE) and human plasma butyrylcholinesterase (BuChE).
• To determine their antiradical properties using DPPH• assay.

Main Methods:

• Synthesis of various 2(5H)-furanone derivatives.
• In vitro evaluation of anticholinesterase activity.
• Free radical scavenging assay using 2,2'-diphenyl-1-picrylhydrazyl (DPPH•).

Main Results:

• Methyl 3-{3-[5,5-disubstituted-4-methyl-3-phenylfuran-2(5H)-ylidene]-1-phenylthioureido}propanoates demonstrated highest selective BuChE inhibition.
• Introduction of a thiocarbamide group enhanced selective antibutyrylcholinesterase activity.
• Dicyanomethylene derivatives exhibited potent antiradical activity (89.1%), surpassing gallic acid and approaching Vitamin C efficacy.

Conclusions:

• Functionally substituted 2(5H)-furanones are promising candidates for anticholinesterase and antiradical agents.
• Structural modifications significantly influence biological activity.
• Further research into these compounds could lead to novel therapeutic agents.