Design, synthesis and preliminary pharmacological evaluation of new non-steroidal anti-inflammatory agents having a 4-(methylsulfonyl) aniline pharmacophore.
A series of 4-(methylsulfonyl)aniline derivatives were synthesized in order to obtain new compounds as a potential anti-inflammatory agents with expected selectivity against COX-2 enzyme. In vivo acute anti-inflammatory activity of the final compounds 11-14 was evaluated in rat using an egg-white induced edema model of inflammation in a dose equivalent to 3 mg/Kg of diclofenac sodium. All tested compounds produced significant reduction of paw edema with respect to the effect of propylene glycol 50% v/v (control group). Moreover, the activity of compounds 11 and 14 was significantly higher than that of diclofenac sodium (at 3 mg/Kg) in the 120-300 minute time interval, while compound 12 expressed a comparable effect to that of diclofenac sodium in the 60-240 minute time interval time, and compound 13 showed a comparable effect to that of diclofenac sodium at all experimental times. The result of this study indicates that the incorporation of the 4-(methylsulfonyl)aniline pharamacophore into naproxen, indomethacine, diclofenac and mefanamic acid maintained their anti-inflammatory activity and may increase selectivity towards the COX-2 enzyme which will be confirmed in the future by assessing COX-2: COX-1 inhibitory ratios using a whole blood assay.
Department of Pharmaceutical Chemistry, College of Pharmacy, University of Baghdad, Baghdad 10047, Iraq. dmfalameri@yahoo.com
Monther Faisel
MF
Mahdi
Mohamed Hassan
MH
Mohammed
Akeel Abdul Kadhum
AA
Jassim
D000814:Aniline Compounds / Q000737:chemistry*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D005260:Female; D008297:Male; D051381:Rats; D017550:Spectroscopy, Fourier Transform Infrared
C572091:4-(methylsulfonyl)aniline; D000814:Aniline Compounds; D000894:Anti-Inflammatory Agents, Non-Steroidal