Synthesis, biological evaluation and docking study of maleimide derivatives bearing benzenesulfonamide as selective COX-2 inhibitors and anti-inflammatory agents.
A series of maleimide analogs bearing benzenesulfonamide were synthesized (4a-r). The anti-inflammatory activity of synthesized derivatives was evaluated using carrageenan induced rat paw edema model. COX-1 and COX-2 potency was evaluated through in vitro cyclooxygenase assays. The results revealed that, compounds 4a, 4h, 4 j, 4 k and 4r had potent COX-2 percentage inhibition as well as in vivo anti-inflammatory activity. The potent compound 4 j was docked into the COX-2 active site to determine the probable binding model. The results of in vivo and in vitro studies demonstrate that phenyl ring with electron withdrawing groups on maleimide ring would generate more potent anti-inflammatory agents. Thus, these compounds can serve as potential leads for further anti-inflammatory studies.
Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Dist Dhule 425 405, India. Electronic address: sandipfirke@rediffmail.com.
Sandip D
SD
Firke
H. R. Patel Institute of Pharmaceutical Education and Research, Shirpur, India.
Sanjay B
SB
Bari
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D002351:Carrageenan; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D015195:Drug Design; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D006801:Humans; D008301:Maleimides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D062105:Molecular Docking Simulation; D051381:Rats; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000096926:Benzenesulfonamides
D000893:Anti-Inflammatory Agents; D002351:Carrageenan; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D008301:Maleimides; D013449:Sulfonamides; D000096926:Benzenesulfonamides; C043592:maleimide
COX-2; Carrageenan paw edema; Docking; Maleimide; Ulcerogenic effects