Sadhana Murali with Galina Bikzhanova and Robert West

Department of Chemistry, UW-Madison

An enzyme called COX-2 (cyclooxygenase-2) is known to be involved in the cause of pain, inflammation, and stiffness related to arthritis.  Previously a number of chemical compounds were synthesized that inhibit the COX-2 enzyme, reducing pain and other problems that are associated with arthritis.  Indomethacin is a nonselective COX-1/COX-2 inhibitor.  The inhibition of COX-1 causes serious side effects such as stomach ulcers and internal bleeding.  There is a need for a compound that selectively inhibits the COX-2 enzyme. 

At Professor West’s group, we synthesized several Indomethacin derivatives that are selective COX-2 inhibitors and are less toxic than Indomethacin.  These Indomethacin derivatives were synthesized through a series of chemical reactions.  The synthesized chemical compounds were isolated and purified by extraction and recrystallization techniques.  Many of the reactions were moisture sensitive and were conducted using the Schlenk line.  Other chemical techniques used were distillation, rotary evaporation, and recrystallization.  All products were analyzed and characterized by 1H, 13C, 29Si NMR spectroscopy.  Through these experiments, a novel Indomethacin derivative was successfully synthesized.  Testing of this new Indomethacin derivative is being carried out.