Evaluation of Anti-nociceptive and Anti-inflammatory Activities of Novel Chalcone Derivatives

Chalcone (1,3-diarylprop-2-en-1-one) derivatives have been introduced as selective cyclooxygenase-2 inhibitors. In the present study, anti-nociceptive and anti-inflammatory effects of eight novel compounds were evaluated in male mice and Wistar rats by using the writhing and formalin-induced paw edema tests respectively. The activities of the compounds were compared with celecoxib as a reference drug. Then, novel compounds were divided into two regioisomeric groups based on the position of the methylsulfonyl substitution. Compounds with substituents such as: 1) H, 2) Me, 3) F and 4) Cl at para position of the phenyl ring of (E)-3-(4-Methanesulfonylphenyl)-1-phenylprop-2-en-1-one were selected in the first group. The regioisomer compounds with 5) H, 6) Me, 7) F and 8) OMe substitutions at C-4 of phenyl ring of (E)-1-(4-Methanesulfonylphenyl)-3-phenylprop-2-en-1-one were chosen as second group. All compounds showed dose-dependent anti-nociceptive activity in writhing test. Interestingly, the potency of anti-nociceptive effect of compounds 1, 2, 5 and 6 were significantly higher than celecoxib. The regioisomeric compounds 1 and 5 with high anti-nociceptive effects, showed a significant dose-dependent anti-inflammatory activity in the paw edema test as well. The results showed that compounds with no substituent or small size substituents at para position of the phenyl ring are the most potent compound in writhing test. Our results revealed that the introduction of a bulky group such as methoxy or chlorine at the vicinal aromatic chain of the derivatives decreases the anti-inflammatory/anti-nociceptive effects. The comparison of estimated ED50 of each pair of the regioisomeric compounds indicates that the relative position of SO2 Me to carbonyl moiety did not affect the potency.