title: Design, synthesis and biological screening of some pyridinylpyrazole and pyridinylisoxazole derivatives as potential anti-inflammatory, analgesic, antipyretic and antimicrobial agents.
abstract: A series of substituted pyridinylpyrazole (or isoxazole) derivatives were synthesized and evaluated for their anti-inflammatory (AI) activity using formalin-induced paw edema bioassays. Their inhibitory activities of cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2) were also determined. The analgesic activity of the same compounds was evaluated using rat-tail withdrawal technique. Their antipyretic activity was also evaluated. The results revealed that compounds 4a,b, 6a, 8a, 14c and 15a exhibited significant AI and analgesic activities. Compounds 5a, 6a and 8a displayed good antipyretic activity. Compounds 14c and 15a showed good COX-2 inhibitory activity and weak inhibition of COX-1. Additionally, the most active compounds were shown to have a large safety margin (ALD50 >300-400 mg / Kg) and minimal ulcerogenic potentialities when administered orally at a dose of 300 mg/Kg. Docking studies for 14c and 15a with COX-2 showed good binding profile. Antimicrobial evaluation proved that most of the compounds exhibited distinctive activity against the gram negative bacteria, P. aeruginosa and E coli.
authors.forename: Soad A M
authors.initials: SA
authors.lastname: El-Hawash
authors.forename: Raafat
authors.initials: R
authors.lastname: Soliman
authors.forename: Amal M
authors.initials: AM
authors.lastname: Youssef
authors.forename: Hanan M A
authors.initials: HM
authors.lastname: Ragab
authors.forename: Perihan A S
authors.initials: PA
authors.lastname: Elzahhar
authors.forename: Ibrahim M
authors.initials: IM
authors.lastname: El-Ashmawey
authors.forename: Abeer E
authors.initials: AE
authors.lastname: Abdel Wahab
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Alexandria, Alexandria, Egypt. soadhawash@yahoo.com.
authors.forename: Iman A
authors.initials: IA
authors.lastname: Shaat
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D058633:Antipyretics / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D004926:Escherichia coli / Q000187:drug effects; D005557:Formaldehyde; D007555:Isoxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D058633:Antipyretics; D007555:Isoxazoles; D011720:Pyrazoles; D011725:Pyridines; D005557:Formaldehyde; D051546:Cyclooxygenase 2