Novel anti-inflammatory agents based on pyrazole based dimeric compounds; design, synthesis, docking and in vivo activity.
Series of pyrazole ester prodrugs analogues have been synthesized and found to contain highly potent inhibitors of the cyclooxygenase-2 (COX-2) enzyme. The paper describes synthesis of the target pyrazole analogues. The structure of the synthesized mutual ester prodrugs (6-8c) were confirmed by (1)H-, (13)C-NMR mass spectroscopy (MS) and their purity were ascertained by TLC and elemental analyses. The biological in vivo evaluation of these compounds in experimental models (carrageenan-induced oedema) proved the presence of anti-inflammatory activity. Docking studies into the catalytic site of COX-2 were used to identify potential anti-inflammatory lead compounds. One lead derivative was chosen endowed with good binding energies.
Tewari
Ashish Kumar
AK
Department of Chemistry, Faculty of Science, Banaras Hindu University, Varanasi 221 005, India. tashish2002@yahoo.com
Srivastava
Priyanka
P
Singh
Ved Prakash
VP
Singh
Amit
A
Goel
Raj Kumar
RK
Mohan
Chethampadi Gopi
CG
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002351:Carrageenan; D020134:Catalytic Domain; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000494:pharmacology; D019281:Dimerization; D015195:Drug Design; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D040521:Subcutaneous Tissue / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D011720:Pyrazoles; D002351:Carrageenan; D051546:Cyclooxygenase 2