Research: DESIGN, SYNTHESIS, AND HYDROLYSIS STUDY OF MUTUAL PRODRUGS OF NSAIDS WITH DIFFERENT ANTIOXIDANTS VIA GLYCOLIC ACID SPACER

Non-steroidal anti-inflammatory drugs (NSAIDs); naproxen and indomethacin have been conjugated with different antioxidants (thymol, guaiacol, and menthol) having antiulcerogenic activity with the objective of obtaining NSAIDs- antioxidant prodrugs as gastrosparing NSAIDs devoid of ulcerogenic side effects. Six mutual prodrugs (1a-c and 2a-c) were synthesized using glycolic acid spacer and their structures were confirmed and characterized using elemental microanalysis (CHNO), IR, and some physiochemical properties. In-vitro chemical and enzymatic hydrolysis studies for naproxen derivatives (1a-c) revealed that these compounds were chemically stable in pH 1.2 and pH 7.4, with t1/2 range from 6.22- 20.98 hr; while in 80% diluted plasma were found to be susceptible to enzymatic hydrolysis with more than 40% hydrolysis occur after 15 min the results indicate higher chemical stability of ester prodrugs in non enzymatic simulated gastro-intestinal fluid and rapid conversion to the parent drugs in 80% human plasma.