Synthesis, Characterization and Anti-Inflammatory Evaluation of New Amino Acids Derivatives of Naproxen

Abstract

Naproxen is well known as a nonsteroidal anti-inflammatory agent that belongs to propionic acid analogs and has the non-selective inhibitory property for both COX1 and COX2, and its side effects belong to the non-selective inhibitory of COX1 in addition to the anti-inflammatory action via COX2 inhibitory. The study aimed to design and synthesize a new Schiff baseof benzaldehyde and thiozolidinone derivative with amino acids spacers like Phenylalanine analogs P4, and Histidine (H5). In silico, the study design was done via auto dock vina soft wave and visualized by UCSF chimera. All analogs showed higher scores of virtual interactions with better affinity to COX2 vs COX1 except the analog P4, which showed a lower score than that of COX1. The chemical synthesis was performed using the conventional synthetic methods of esterification of amino acids, the insertion of hydrazine hydrate to the amino acids esters to get hydrazide, the reaction of benzaldehyde or anisaldehyde with hydrazide to get Schiff base, the reaction of Schiff base with mercaptoacetic acid to get Thiozolidinone, and finally the amidation of Naproxen to get the final analogs, the structural specification and characterization was introduced by FTIR, 1HNMR and 13Cspectroscopy. The biological evaluation of the newly synthesized analogs was done through induction paw edema, calculating the decrease in paw thickness in comparison with negative control DMSO and positive control naproxen. These results showed that all analogs got better anti-inflammatory action thanNaproxen; the best result was for the analog P4, which showed more powerful anti-inflammatory action than the others with a significant p-value (0.008 as compared with Naproxen)