Synthesis and preliminary pharmacological study of sulfonamide conjugates with ibuprofen and indomethacin as new anti-inflammatory agents

الملخص EN

4-aminobenzenesulfonamide conjugates of ibuprofen (compound 10) and indomethacin (compound 11) have been designed and synthesized by the reaction of sulfanilamide (compound 7) with 2-(4-isobutylphenyl) propanoic acid (ibuprofen) and 2-(1-(4-chlorobenzoyl)-5-1methoxy-2-methyl-H-indol-3-yl)acetic acid (indomethacin) for the evaluation as potential anti-inflammatory agents with expected selectivity against COX-2 enzyme.

In vivo acute anti-inflammatory activity of the synthesized final compounds (10 and 11) was evaluated in rats using egg-white induced edema model of inflammation in a dose equivalent to (10mg / Kg) of ibuprofen and (2mg / kg) of indomethacin.

The tested compounds produced significant reduction of the rat paw edema with respect to the effect of propylene glycol 50 % v / v (control group).

Moreover, compound (10) exhibited comparable anti-inflammatory activity to diclofenac (3mg / Kg) (reference group) while compound (11) exhibited less anti-inflammatory activity than diclofenac.

The result of this study indicate that the incorporation of the 4-aminobenzenesulfonamide pharmacophore into ibuprofen and indomethacin maintained their anti-inflammatory activity and may increase their selectivity toward COX-2 enzyme which can be confirmed in future by assessing COX-2 : COX-1 inhibitory ratio.