Arylhydrazone derivatives of naproxen as new analgesic and anti-inflammatory agents: Design, synthesis and molecular docking studies

• Please check the hierarchy of the section headings and amend if necessary.
• Their binding affinities to COX enzymes were evaluated by docking studies.
• The docking results showed that the compounds bind more selectively to COX-2.
• The designed compounds were synthesized and their pharmacological activities were evaluated.

A series of new arylidenehydrazone derivatives of naproxen were synthesized and evaluated for their analgesic and anti-inflammatory activities. Some of the synthesized analogues showed comparable activities when compared against naproxen for their analgesic and anti-inflammatory properties. 2-(6-methoxy-2-naphthyl)-N′-[(pyridine-4-yl)methylene]propanoic acid hydrazide 4j was found to be the most active analgesic agent. 2-(6-methoxy-2-naphthyl)-N′-[4-nitrobenzylidene]propanoic acid hydrazide 4g showed highest anti-inflammatory activity in comparison to the naproxen. Molecular modeling study of the synthesized compounds suggested that the designed molecules were well located and bound to the COX-1 and COX-2 active sites. Compound 4g showed the highest selectivity for COX-2 (RCOX-2/COX-1 = 1.94) and higher affinity rather than naproxen in COX-2 active site (RCOX-2/naproxen = 1.28). Moreover, the structural analyses confirmed that the E-ap rotamer is the preferred structure for the arylidenehydrazone derivatives.

Figure optionsDownload high-quality image (204 K)Download as PowerPoint slide