Design, synthesis, and SAR studies of some 5-aliphatic oximino esters of thiophene as potential anti-inflammatory leads: comparative biological activity profile of aliphatic oximes vs aromatic oximes.

Abstract

A series of novel tetra substituted thiophenes were synthesized, characterized, and evaluated for their anti-inflammatory activity in carrageenin induced rat paw edema model-an acute in vivo model. Compounds V1, V3, V11, V12, V17, and V18 showed good anti-inflammatory activity, indicating the importance of oxime moiety in modulating the activity. The structure-activity relationship studies explore "the aliphatic oxime esters" attached via a ketone bridge to fifth position of the thiophene, and indicate that this feature may enhance the anti-inflammatory activity as compared to aromatic oximes. Since free radicals are implicated in various inflammatory disorders, the free radical scavenging activity of some of the synthesized candidates was assessed using 1,1-diphenyl-2-picryl hydrazyl assay. The oxime containing analogs exhibited weak to moderate activity as free radical scavengers in DPPH assay. A plausible reasoning for its free radical scavenging ability is discussed. All the compounds were also screened in nitro blue tetrazolium model, to assess them as superoxide anion radical scavengers. A direct correlation between anti-inflammatory activity and free radical scavenging activity was not seen. The results disclose a new class of anti-inflammatory agents designed and synthesized for the first time wherein the utility of aliphatic oxime esters in modulating the anti-inflammatory activity profile is apparent. This will give us potential anti-inflammatory leads.

• Authors: Ajay D Pillai, Parendu D Rathod, P X Franklin, Harish Padh, Kamala K Vasu, V Sudarsanam
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 317 Issue 4 Pg. 1067-74 (May 14 2004) ISSN: 0006-291X [Print] United States
• PMID: 15094377 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Biphenyl Compounds
• Esters
• Free Radical Scavengers
• Hydrocarbons, Aromatic
• Oximes
• Picrates
• Thiophenes
• 1,1-diphenyl-2-picrylhydrazyl

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (chemical synthesis, chemistry, pharmacology)
• Biphenyl Compounds
• Disease Models, Animal
• Drug Design
• Edema (chemically induced, drug therapy)
• Esters (chemistry)
• Free Radical Scavengers (chemistry, pharmacology)
• Hydrocarbons, Aromatic (chemistry)
• Molecular Structure
• Oximes (chemistry, pharmacology)
• Picrates (metabolism)
• Rats
• Structure-Activity Relationship
• Thiophenes (chemical synthesis, chemistry, pharmacology)