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

Authors

MECİT ORHAN ULUDAĞ
BURCU ÇALIŞKAN ERGÜN
DUYGU ASLI ALKAN
NİLÜFER ERCAN
GÜLER YAĞMUR ÖZKAN
ERDEN BANOĞLU

DOI

10.3906/kim-1010-732

Abstract

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.

Keywords

Ibuprofen, ketoprofen, mefenamic acid, writhing, carrageenan

First Page

427

Last Page

439

Recommended Citation

ULUDAĞ, MECİT ORHAN; ERGÜN, BURCU ÇALIŞKAN; ALKAN, DUYGU ASLI; ERCAN, NİLÜFER; ÖZKAN, GÜLER YAĞMUR; and BANOĞLU, ERDEN (2011) "Stable ester and amide conjugates of some NSAIDs as analgesic and antiinflammatory compounds with improved biological activity," Turkish Journal of Chemistry: Vol. 35: No. 3, Article 7. https://doi.org/10.3906/kim-1010-732
Available at: https://journals.tubitak.gov.tr/chem/vol35/iss3/7