Synthesis, characterization, docking studies and anti-inflammatory activity of new safe NSAIDs agent based on Ibuprofen phenylalanine derivatives

Document Type : Original Article

Authors

1 Chemistry Department, Faculty of Science, Al-Azhar University (Boys' Branch), Nasr City, Cairo, Egypt

2 Department of Chemistry of Natural and Microbial Products, National Research Centre, Dokki, P.O. 12622, Giza, Egypt

3 Department of Pharmacology, Toxicology and Biochemistry, Future University in Egypt, Cairo, Egypt.

4 Chemistry Department, Faculty of Science, Al-Azhar University (Boys' Branch), Nasr City, Cairo, Egypt

Abstract

Ibuprofen phenylalanine derivatives 1-17 as new safe nonsteroidal anti-inflammatory drugs (NSAIDs) agents were synthesized and characterized depending on spectroscopic and analytical analyses. Starting from reaction between ibuprofen with PABA to have fussed derivative 1 that reacted with phenylalanine followed by hydrazine, ammonium thiocyanate, urea derivatives to afford the new compounds. For investigated drugs 1-17, molecular docking was done at the cyclooxygenase-2 (COX-2) active site. For the purpose of discussing binding affinity, the position with the lowest root-mean square deviation (RMSD) has been chosen. The binding interaction was enhanced by adding a hydrazide fragment to the parent molecule, as shown in the docking technique. Compounds 5, 6, 12, 16 and 17 were investigated as anti-inflammatory and analgesic drugs. Using a carrageenan-induced mice of hind paw edoema, we investigated the synthesized compounds' potential anti-inflammatory activity in contrast to their parent molecule, ibuprofen. The antinociceptive and the ulcerogenic effect of the synthesized compounds have been measure. Compounds 5 and 6 are the best drug analogues and these compounds could be promising for anti-inflammatory agents.

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