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

作者：Azizian Homa; Mousavi Zahra; Faraji Hamidreza; Tajik Mohammad; Bagherzadeh Kowsar; Bayat Peyman; Shafiee Abbas; Almasirad Ali^*

来源：Journal of Molecular Graphics and Modelling, 2016, 67: 127-136.

DOI：10.1016/j.jmgm.2016.05.009

• Hydrazone
• Cyclooxygenase
• Molecular modeling
• Anti-inflammatory
• Analgesic
• AutodockVina

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.

• 出版日期2016-6