Synthesis and anti-inflammatory activity of novel (substituted)benzylidene acetone oxime ether derivatives: molecular modeling study.
Herein, we report the design, synthesis, and pharmacological properties of a series of substituted benzylidene acetone oxime ether derivatives from the corresponding oxime derivatives. All the newly synthesized compounds were investigated in vivo for their anti-inflammatory activities using carrageenin-induced rat paw oedema model. Among the compounds examined, compounds 5b and 7a showed the highest activity, nearly equivalent to that of the standard drug diclofenac sodium. Hence, they were screened for their analgesic activities using acetic acid-induced writhing model in mice and also, their ulcerogenic effects were studied. Compound 7a was found to possess significant anti-inflammatory and analgesic activities with negligible ulcerogenic effect. Docking study of the synthesized compound 7a into the active site of COX-1 and COX-2 revealed a similar binding mode to SC-558, a selective COX-2 inhibitor.
El-Gamal
Mohammed I
MI
Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt.
Bayomi
Said M
SM
El-Ashry
Saadia M
SM
Said
Shehta A
SA
Abdel-Aziz
Alaa A-M
AA
Abdel-Aziz
Naglaa I
NI
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002074:Butanones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004987:Ethers; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010091:Oximes / Q000737:chemistry*; D051381:Rats; D013055:Spectrophotometry, Infrared; D013816:Thermodynamics
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002074:Butanones; D004987:Ethers; D010091:Oximes; C025383:benzylideneacetone