Green extraction of methylxanthine derivatives from food and beverages using deep eutectic solvents and in silico studies of neuroprotective potential

In the food and pharmaceutical industries, green technologies refer to the use of methods and materials that do not negatively impact the environment and offer safety advantages. The aim of this paper is to extract methylxanthine derivatives from food and beverage samples using ultrasound-assisted deep eutectic solvent extraction (UAE-DES), ultrasound (UAE), and microwave-assisted extraction (MAE), and traditional extraction with chloroform. A chemometric tool was applied for data analysis and molecular docking was used to predict neuroprotective potential. The high-performance liquid chromatography (HPLC) method was employed for methylxanthines determination. The results showed that green approaches effectively extracted theobromine (1,3-dimethylxanthine) and caffeine (1,3,7-trimethylxanthine) from food and beverages, with UAE-DES emerging as the most effective technique. Caffeine's high binding energy (–6.7 kcal/mol) against the adenosine receptor (A2A) observed by molecular docking suggested that it may have neuroprotective effects and could be used in multiple fields with promising future development possibilities. According to the results, the application of DESs as high dissolving, low cost, and environmental-friendly solvents has significant potential in the pharmaceutical and food industry.