Mechanism of action in a 4,5-diarylpyrrole series of selective cyclo-oxygenase-2 inhibitors

Using semi-empirical AM1 calculation and 6.31G* basis sets, we have calculated the energy of the highest-occupied molecular orbital (EHOMO) for anti-inflammatory 4,5-diarylpyrroles which have been shown to have inhibitory activity on cyclooxygenase COX-2, an inducible enzyme expressed during inflammation. We have found a correlation between the EHOMO of a molecule and its COX-2 inhibition. However, no correlation was observed between EHOMO and the inhibition efficiency of cyclooxygenase-1 (COX-1), the constitutively expressed enzyme, protective to the organism. This result suggests that the inhibitions of the two isoforms follow different molecular mechanisms.