Synthesis, Characterization, ADME Study and In-Vitro Anti-Inflammatory Activity of Aspirin Amino Acid Conjugates

This work was aimed at synthesising and characterising five new conjugates of aspirin with aromatic amino acids and testing them in vitro as potential selective cyclooxygenase 2 (COX-2) inhibitors. The conjugates were synthesized by a 3-step approach and successfully characterized by analyzing their H-1 and C-13 NMR and optical spectra. The in vitro activity was tested against COX-1 and COX-2 using celecoxib and aspirin as control drugs, and the ADME properties were investigated through SwissADME web tool. All the synthesized conjugates were less active than aspirin on COX-1 and more active on COX-2, and 3 of them (compounds Y1, Y3 and Y5) showed activity and selectivity comparable to those of celecoxib. SwissADME predicted that the conjugates would have high gastrointestinal absorption and better synthetic accessibility than celecoxib. They did not score any violation from the drug-likeness filters as well. Being composed of well-known molecules, these conjugates offer the advantage of being safe and easy to synthesize potential selective inhibitors of COX-2.

Automated summary

This study aimed to synthesize and characterize five new aspirin conjugates with aromatic amino acids, and test their in vitro effects as potential selective cyclooxygenase 2 (COX-2) inhibitors. The conjugates were successfully synthesized and characterized through analysis of their H-1 and C-13 NMR and optical spectra. In vitro activity testing showed that the synthesized conjugates had lower activity than aspirin on COX-1 but higher activity on COX-2. Three of the conjugates (compounds Y1, Y3, and Y5) demonstrated comparable activity and selectivity to celecoxib. The SwissADME web tool predicted that the conjugates had high gastrointestinal absorption and better synthetic accessibility than celecoxib, and they also met the drug-likeness filters.