Background: Nonsteriodal anti-inflammatory drugs (NSAIDs) are numerous and widely
used for more than 60 years, but there is still a strong need for developing novel selective NSAIDs.
The need is justified by the fact that nonselective NSAIDs can produce serious gastric side effects
and that some of the selective NSAID are withdrawn due to their cardiotoxic side effects.
Methods: Eight β-hydroxy-β-arylpropanoic acids, which belong to the arylpropanoic acid class of
compounds, structurally similar to some nonsteroidal anti-inflammatory drugs (NSAIDs), were
docked into 3D catalytic site of both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2).
Seven out of those eight acids were synthesized using already published modification of Reformatsky
reaction additionally optimized by increasing temperature. Synthesized compounds were
tested in vivo in order to elucidate anti-inflammatory activity, gastric tolerability and impact on liver
function of rats.
Results: Results of docking studies have indicated that all compounds have potential to selectively
inhibit COX-2 isoform, but that the compounds containing polar substituents on phenyl ring are better
inhibitors. Results of carrageenan-induced rat paw oedema test have shown that all compounds
exhibit dose dependence and good gastric tolerability and none of the tested compounds have shown
negative effect on liver function compared to ibuprofen.
Conclusion: The compound containing polar nitro group in para position has shown the best docking
results, anti-inflammatory activity, low hepatotoxicity and good gastric tolerability.