title: Synthesis and biological evaluation of new pyrazolone-pyridazine conjugates as anti-inflammatory and analgesic agents.
abstract: A new series of pyrazolone-pyridazine conjugates 3 and 4a-l were synthesized and characterized by spectroscopic means and elemental analyses. All compounds were tested in vivo for their anti-inflammatory and analgesic properties against diclofenac, as reference compound. The synthesized compounds were also evaluated for their ability to inhibit the production of certain inflammatory cytokines such as TNF-α and IL-6 in serum samples. The ulcerogenic potential of the synthesized compounds was also determined. IC50 values for inhibition of COX-1 and COX-2 enzymes were investigated in vitro for the most active candidates. Molecular docking was performed on the active site of COX-2 to predict their mode of binding to the amino acids. Among the synthesized derivatives, compounds 4c and 4e showed good analgesic and anti-inflammatory activities with lower ulcer index than the reference drug.
authors.affiliation: Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr Elini st., Cairo 11562, Egypt.
authors.forename: Nadia Abdalla
authors.initials: NA
authors.lastname: Khalil
authors.affiliation: Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr Elini st., Cairo 11562, Egypt.
authors.forename: Eman Mohamed
authors.initials: EM
authors.lastname: Ahmed
authors.affiliation: Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr Elini st., Cairo 11562, Egypt.
authors.forename: Khaled Omar
authors.initials: KO
authors.lastname: Mohamed
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt. Electronic address: yassin.nissan@hotmail.com.
authors.forename: Yassin Mohammed
authors.initials: YM
authors.lastname: Nissan
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.
authors.forename: Sawsan Abo-Bakr
authors.initials: SA
authors.lastname: Zaitone
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002351:Carrageenan; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D047069:Pyrazolones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011724:Pyridazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D047069:Pyrazolones; D011724:Pyridazines; C038362:pyrazolone; C062482:pyridazine; D002351:Carrageenan; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2
keywords: Analgesic; Anti-inflammatory; Pyrazolone; Pyridazine