Arylhydrazone derivatives of naproxen as new analgesic and anti-inflammatory agents: Design, synthesis and molecular docking studies.
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.
Department of Medicinal Chemistry, Pharmacy School, International Vice Chancellor Office, Iran University of Medical Sciences, Tehran, Iran.
Homa
H
Azizian
Department of Pharmacology & Toxicology, Faculty of Pharmacy,Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran.
Zahra
Z
Mousavi
Department of Pharmacology & Toxicology, Faculty of Pharmacy,Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran.
Hamidreza
H
Faraji
Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Mohammad
M
Tajik
Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran.
Kowsar
K
Bagherzadeh
Department of Medicinal Chemistry, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran.
Peyman
P
Bayat
Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Abbas
A
Shafiee
Department of Medicinal Chemistry, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran. Electronic address: almasirad.a@iaups.ac.ir.
Ali
A
Almasirad
D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D020134:Catalytic Domain; D003460:Crystallization; D051545:Cyclooxygenase 1 / Q000737:chemistry; D051546:Cyclooxygenase 2 / Q000737:chemistry; D015195:Drug Design; D006835:Hydrazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008024:Ligands; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D009288:Naproxen / Q000737:chemistry / Q000494:pharmacology*; D017208:Rats, Wistar; D015203:Reproducibility of Results; D016415:Sequence Alignment; D013816:Thermodynamics
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D006835:Hydrazones; D008024:Ligands; D009288:Naproxen; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2
Analgesic; Anti-inflammatory; AutodockVina; Cyclooxygenase; Hydrazone; Molecular modeling