Stable ester and amide conjugates of some NSAIDs as analgesic and antiinflammatory compounds with improved biological activity

ULUDAĞ M. O., Ergun B., Alkan D. A., Ercan N., Ozkan G. Y., BANOĞLU E.

Turkish Journal of Chemistry, cilt.35, sa.3, ss.427-439, 2011 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 35 Sayı: 3
  • Basım Tarihi: 2011
  • Doi Numarası: 10.3906/kim-1010-732
  • Dergi Adı: Turkish Journal of Chemistry
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, TR DİZİN (ULAKBİM)
  • Sayfa Sayıları: ss.427-439
  • Anahtar Kelimeler: Ibuprofen, ketoprofen, mefenamic acid, writhing, carrageenan, ANTI-INFLAMMATORY DRUGS, DIFFERENTIAL INHIBITION, CLINICAL-SIGNIFICANCE, DERIVATIVES, INDOMETHACIN, PRODRUGS, IBUPROFEN, DESIGN, POTENT, ACIDS
  • Gazi Üniversitesi Adresli: Evet

Özet

A set of ester and amide derivatives of some acidic NSAIDs, including ibuprofen, ketoprofen, and mefenamic acid (1-3), were synthesized and evaluated for their in vivo analgesic and antiinflammatory activity using the p-benzoquinone-induced writhing test and the carrageenan-induced paw edema model, respectively. Among the synthesized compounds, ester derivatives of ketoprofen showed especially potent analgesic and antiinflammatory activity as compared to the parent drug. In vitro chemical stability studies revealed that ester and amide derivatives were chemically stable in simulated gastric (pH 1.2) and intestinal fluids (pH 6.8). In 80% human plasma, the ester derivatives were found to be relatively stable against plasma esterases over periods of 24 h, indicating that the observed activity was not due to the parent NSAIDs. Most of the compounds were found to be nonulcerogenic under the tested conditions. © TÜBİTAK.