Synthesis and biological activities of novel dexibuprofen tetraacetylriboflavin conjugates

A series of novel dexibuprofen derivatives covalently linked via alkylene spacers of variable length to tetraacetylated riboflavin have been developed. The target compounds became accessible by reaction of the chloromethyl ester of dexibuprofen with tetraacetylriboflavin (compound 7) or by synthesis of the appropriate N3-(omega-iodoalkyl)-2',3',4',5'-Tetraacetylriboflavin followed by treatment with dexibuprofen (derivatives 8-11), respectively. Biological screening revealed that the target compounds exhibit antiproliferative effects on MCF-7 breast cancer and HT-29 colon carcinoma cells with IC50 values in the range of 8-15 microM. Enzymatic studies on human platelets indicated significant COX-1 inhibitory activities of the target compounds.