Synthesis and cyclooxygenase inhibitory activities of some N-acylhydrazone derivatives of isoxazolo[4,5-d]pyridazin-4(5H)-ones.
In this study, new isoxazolo[4,5-d]pyridazin-4(5H)-one derivatives having an N-acylhydrazone moiety were synthesized. The compounds were tested for their COX inhibitory activities using NS-398 and indomethacine as reference compounds. Although the compounds had an inhibitory profile against both COX-1 and COX-2, most were found to be more selective against COX-2 by a small percentage of inhibition, at the concentration of 50 microM. Docking studies were done to understand the interactions of the tested compounds with the active site of COX-2. It was observed that the compounds fit into, and interacted with, the hydrophobic parts which are common in the active pocket of COX-1 and COX-2 enzymes but could not fit to the area which is specific for COX-2 enzyme.
Unsal-Tan
Oya
O
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Hacettepe, Ankara, Turkey. oyaunsal@hacettepe.edu.tr
Ozden
Kevser
K
Rauk
Arvi
A
Balkan
Ayla
A
D000818:Animals; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011724:Pyridazines / Q000737:chemistry*
D016861:Cyclooxygenase Inhibitors; D006835:Hydrazones; D011724:Pyridazines; C062482:pyridazine; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases