title: Synthesis, cyclooxygenase inhibition and anti-inflammatory evaluation of new 1,3,5-triaryl-4,5-dihydro-1H-pyrazole derivatives possessing methanesulphonyl pharmacophore.
abstract: A new series of 1,3,5-triaryl-4,5-dihydro-1H-pyrazole derivatives 13a-p were synthesized via aldol condensation of 3/4-nitroacetophenones with appropriately substituted aldehydes followed by cyclization of the formed chalcones with 4-methanesulfonylphenylhydrazine hydrochloride. All the synthesized compounds were evaluated for their cyclooxygenase (COX) inhibition, anti-inflammatory activity and ulcerogenic liability. All compounds were more potent inhibitors for COX-2 than COX-1. While most compounds showed good anti-inflammatory activity, compounds 13d, 13f, 13k and 13o were the most potent derivatives (ED50 = 66.5, 73.4, 79.8 and 70.5 μmol/kg, respectively) in comparison with celecoxib (ED50 = 68.1 μmol/kg). Compounds 13d, 13f, 13k and 13o (ulcer index = 3.89, 4.86, 4.96 and 3.92, respectively) were 4-6 folds less ulcerogenic than aspirin (ulcer index = 22.75) and showed approximately ulceration effect similar to celecoxib (ulcer index = 3.35). In addition, molecular docking studies were performed for compounds 13d, 13f, 13k and 13o inside COX-2 active site which showed acceptable binding interactions (affinity in kcal/mol -2.1774, -6.9498) in comparison with celecoxib (affinity in kcal/mol -6.5330).
authors.affiliation: a Department of Pharmaceutical Organic Chemistry , Beni-Suef University , Beni-Suef , Egypt .
authors.forename: Khaled R A
authors.initials: KR
authors.lastname: Abdellatif
authors.affiliation: b Department of Medicinal Chemistry , Beni-Suef University , Beni-Suef , Egypt , and.
authors.forename: Mohammed T
authors.initials: MT
authors.lastname: Elsaady
authors.affiliation: c Department of Pharmaceutical Medicinal Chemistry , Al-Azhar University , Assuit , Egypt.
authors.forename: Salah A
authors.initials: SA
authors.lastname: Abdel-Aziz
authors.affiliation: c Department of Pharmaceutical Medicinal Chemistry , Al-Azhar University , Assuit , Egypt.
authors.forename: Ahmed H A
authors.initials: AH
authors.lastname: Abusabaa
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D008297:Male; D066244:Proton Magnetic Resonance Spectroscopy; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013055:Spectrophotometry, Infrared
chemical_list: D000893:Anti-Inflammatory Agents; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles
keywords: Anti-inflammatory; cyclooxygenase inhibition; dihydropyrazole