Design, synthesis, and acute anti-inflammatory assessment of new ketoprofen analogs having 4-thiazolidinone nucleus

Abstract

Ketoprofen is well known non-selective non-steroidal anti-inflammatory drug possess different side effects, the major one is the gastric irritation and ulceration due to the presence of free carboxyl group in the chemical structure in addition to lack of selectivity in its action by the inhibition of COX-1 enzyme which is required for the pro- duction of cytoprotective prostaglandins. This study aims to reduce the effects by conversion the carboxylic group into a thiazolidinone ring to reduce the direct side effects and increasing its selectivity toward COX-2 enzyme through increased bulkiness by using GABA as spacer, in which the Preferential inhibition of COX-2 is thought to be due to the additional space in the COX-2 hydrophobic channel, as well as to the presence of a side pocket in the channel. The preliminary anti-inflammatory study has revealed that Ve & Vf having better anti-inflammatory activity than ketoprofen. Number of docking results of synthesized compounds have surpassed the docking score of celecoxib as control. Incorporation of 4-Thiazolidinone pharmacophore into a ketoprofen maintained or enhanced it is anti-inflammatory activity.