title: Evaluation of anti-inflammatory, analgesic activities, and side effects of some pyrazole derivatives.
abstract: OBJECTIVE
  Non-steroidal anti-inflammatory drugs are associated with several side effects, such as gastrointestinal mucosal damage, renal toxicity, and cardiovascular side effects. Aiming to find a novel analgesic/anti-inflammatory drug with minimal side effects, the present study was designed to screen and evaluate some newly synthesized pyrazole derivatives.
  
  
  METHODS
  Anti-inflammatory activity using carrageenan-induced rat paw edema and cotton-pellet-induced granuloma, COX-1/COX-2 selectivity using thin layer chromatography, and analgesic using hot plate and tail flick tests as well as ulcerogenic and renal side effects of the ten compounds were assessed.
  
  
  CONCLUSIONS
  The results of the carrageenan-induced rat paw edema showed that the carboxyphenylhydrazone derivative (N9) was more potent than the chlorophenyl counterpart (N8) with a relative activity compared to celecoxib of 1.08 and -0.13, respectively, after 1 h. Even though this is true, N9 caused significant increase in the ulcer index, creatinine, and Blood Urea Nitrogen levels. The cotton granuloma test showed that the carboxyphenylhydrazone derivative (N7) was also more potent than its chlorophenyl counterpart (N6) with a relative activity compared to celecoxib of 1.13 and 0.86, respectively. Moreover, adding an acetyl not only increased the anti-inflammatory activity from a relative activity compared to celecoxib of 0.57-1.17 for the compounds X4 and N5, respectively, in the granuloma test, but also increased the selectivity toward COX-2 from 0.197 to 47.979.
  
  
  CONCLUSIONS
  As a conclusion, from the ten compounds analyzed, N5 and N7 showed promising results as anti-inflammatory/analgesic agents with low ulcerogenicity and nephrotoxicity and thus should be further analyzed to determine the ED50 and other side effects.
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Beirut Arab University, Beirut Campus, Tareek El Jadida, Riad El Solh, P.O. Box 11-5020, Beirut, 11072809, Lebanon. t.domyati@bau.edu.lb.
authors.forename: Souraya
authors.identifier: http://orcid.org/0000-0002-6423-5488
authors.initials: S
authors.lastname: Domiati
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Pharos University, Alexandria, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: El-Mallah
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Damanhur University, Damanhur, Egypt.
authors.forename: Asser
authors.initials: A
authors.lastname: Ghoneim
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
authors.forename: Adnan
authors.initials: A
authors.lastname: Bekhit
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
authors.forename: Heba Abd
authors.initials: HA
authors.lastname: El Razik
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; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004487:Edema / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology; D005753:Gastric Mucosa / Q000187:drug effects; D006099:Granuloma / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology; D007668:Kidney / Q000187:drug effects; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D011720:Pyrazoles / Q000009:adverse effects* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017208:Rats, Wistar
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011720:Pyrazoles; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2
keywords: Cyclooxygenase; Inflammation; Non-steroidal anti-inflammatory drugs; Pyrazole derivatives