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Abstract

DESIGN AND SYNTHESIS OF NEW DERIVATIVES OF KETOPROFEN LINKED TO NATURAL ANTIOXIDANTS (THYMOL, MENTHOL & GUAIACOL) AS POSSIBLE MUTUAL PRODRUGS

Dhurgham Q. Shaheed, Ahmed Kareem Hussein Mubarak*, Ammar Abdul Aziz libeg, Hayder Kadhium Abbas, Mohammed Dakhil ALRekabi, Ahmed Hashim Husssein

ABSTRACT

Non-steroidal anti-inflammatory drugs (NSAIDs) represent one of the most widely used classes of drugs. They are used primarily for the treatment of osteoarthritis, rheumatoid arthritis and other inflammatory disorders. However, the use of NSAIDs is limited due to possibility of inducing erosions and ulcers in the gastrointestinal tract. Recently, it has been well established that generation of various reactive oxygen species (ROS) locally plays a significant role in the formation of gastric ulceration associated with NSAID therapy. Therefore, in the present study NSAIDs (ketoprofen) have been conjugated with different antioxidants (thymol, menthol and guaiacol) having anti ulcerogenic activity. The objective was to obtain Ketoprfen– antioxidant derivatives as possible mutual prodrug that includes: Ketoprofen-thymol (Compound I), Ketoprofen-menthol (Compound II) and Ketoprofen - guaiacol (Compound III). The mutual prodrug of NSAID and antioxidant was designated to generate the complementary pharmacological action as a single chemical entity with improved anti-inflammatory action and reduced ulcerogenic adverse effect. The synthesis is conferred by FT-IR, CHNS and physiochemical properties.

Keywords: Ketoprofen, Thymol, Menthol, Guaiacol, Mutual prodrug.


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