Chiral 2-aryl-propionic acid derivatives (2-APAs) belong to the group of non-steroidal anti-inflammatory drugs (NSAIDs) and are one of the most frequently used medicines in the treatment of acute and chronic pain, rheumatic disorders, and to moderate pain and fever. The propionic acid side-chain of the 2-APAs possesses an asymmetric a-carbon atom and therefore 2-APAs exist in two enantiomeric forms of the (+)-S and (-)-R. In vivo (-)-R-enantiomer of some 2-APAs undergoes a unidirectional bioinversion to the (+)-S enantiomer. In this molecular mechanism (-)-R enantiomer is initially converted into its coenzyme A thioester and subsequently the (-)-R thioester epimerazes to the (+)-S-thioester. The sequence is completed with the hydrolysis of the thioester. In result of the chiral inversion of R to S the pharmacokinetic properties of the two ibuprofen enantiomers in human are also changed. However, the effects observed for the (-)-R enantiomers of flurbiprofen and ketoprofen are different. The (-)-R-flurbiprofen does not undergo chiral inversion in man, but the (-)-R-ketoprofen is inversed in small range, and therefore they can be administered in pure enantiomeric form. The anti-inflammatory activity of 2-APAs, as determined by non-selective inhibition of prostaglandin cyclooxygenase, COX-1 and COX-2 resides almost exclusively in (+)-S enantiomer. Recent investigations indicate that (-)-R enantiomer of 2-APAs is not devoided of any pharmacodynamic activity. It contributes to the analgesic activity of the racemic mixtures of the ketoprofen. Moreover, (-)-R enantiomers of ibuprofen and flurbiprofen inhibit synthesis of b-amyloid peptide, the agent connected with Alzheimer’s disease. The (-)-R-flurbiprofen has also reduced formation of colon and prostate cancer in animal models. The recent studies on estimation of apoptosis of neutrophils, via caspase-3, treated with flurbiprofen, indobufen, ketoprofen or naproxen let us know that enantiomers as well racemates of the above compounds induce apoptosis of polymorphonuclear leucocytes (PMNs). The maximal effect on apoptosis of PMNs was achieved for flurbiprofen. The differences in pharmacological mechanisms of activity of enantiomers and resulting from that potential utility of single enantiomers or racemic forms in prevention and treatment of some serious diseases will be presented.

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