title: Synthesis, molecular docking and biological evaluation of some newer 2-substituted-4-(benzo[d][1,3]dioxol-5-yl)-6-phenylpyridazin-3(2H)-ones as potential anti-inflammatory and analgesic agents.
abstract: A new series of 2-substituted-4-(benzo[d][1,3]dioxol-5-yl)-6-phenylpyridazin-3(2H)-one derivatives has been synthesized and studied. The in vivo anti-inflammatory and analgesic activities of the synthesized compounds were evaluated using carrageen rat paw edema model and acetic acid induced writhing model, respectively. Side effect profile of the newly synthesized pyridazinones was assessed by gastric ulcerogenic and anti-platelet activity. The compounds were further evaluated for their inhibitory activity against cyclooxygenase enzyme (COX-1/COX-2) by in vitro colorimetric COX (ovine) inhibitor screening assay method. The p-flourophenylpiperazine substituted analogue 14 exhibited most potent anti-inflammatory and analgesic activities with lower ulcer index and extremely good selectivity towards COX-2 versus COX-1 enzyme with a selectivity index of 10. Molecular docking studies showed appreciable binding of new pyridazinone analogues with the amino acids present at the active site of hCOX-2 enzyme.
authors.affiliation: University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Singh
authors.affiliation: Centre for Bioinformatics, M.D University, Rohtak, Haryana, India.
authors.forename: Vandana
authors.initials: V
authors.lastname: Saini
authors.affiliation: Centre for Bioinformatics, M.D University, Rohtak, Haryana, India.
authors.forename: Ajit
authors.initials: A
authors.lastname: Kumar
authors.affiliation: University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India. Electronic address: ranju29in@yahoo.co.in.
authors.forename: Ranju
authors.initials: R
authors.lastname: Bansal
mesh_terms: D000700:Analgesics / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects; D002351:Carrageenan; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D006801:Humans; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D011724:Pyridazines / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D011724:Pyridazines; C068053:5,6-diphenylpyridazin-3-one; D002351:Carrageenan; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2
keywords: Analgesic; Anti-inflammatory; Anti-platelet; Molecular docking; Pyridazinone; Ulcer index