title: Synthesis, anti-inflammatory, cyclooxygenases inhibitions assays and histopathological study of poly-substituted 1,3,5-triazines: Confirmation of regiospecific pyrazole cyclization by HMBC.
abstract: Three novel triazines series were prepared. These series are pyrazolines (4a and 4b), pyrazoles (6a, 6b and 8a-d) and isoxazoles (7a and 7b). Such series were designed as COX-2 inhibitors. All compounds were characterized by using spectroscopic methods and elemental analysis. Regarding COX-2, compounds 5b, 4a and 3b were the most active with IC50in the range of 0.55-0.87 μM. Most of synthesized compounds were relatively more potent to celecoxib (0.78 μM), diclofenac (2.94 μM) and indomethacin (7.24 μM). A molecular modeling study was performed for the most active compounds. Histopathological evaluation also was done to estimate the safety of compounds. Finally, structure elucidation of pyrazole 8 was studied by 2D NMR.
authors.affiliation: Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt.
authors.forename: Heba A H
authors.initials: HAH
authors.lastname: Elshemy
authors.affiliation: Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt. Electronic address: eman.ahmed@pharm.bsu.edu.eg.
authors.forename: Eman K A
authors.initials: EKA
authors.lastname: Abdelall
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt.
authors.forename: Amany A
authors.initials: AA
authors.lastname: Azouz
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt.
authors.forename: Abeer
authors.initials: A
authors.lastname: Moawad
authors.affiliation: Biochemistry Lab, Cairo General Hospital, Cairo, Egypt.
authors.forename: Waleed A M
authors.initials: WAM
authors.lastname: Ali
authors.affiliation: Department of Pathology, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef, 62514, Egypt.
authors.forename: Nesreen M
authors.initials: NM
authors.lastname: Safwat
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D003500:Cyclization; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D015195:Drug Design; D008297:Male; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D011720:Pyrazoles / Q000737:chemistry*; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014227:Triazines / Q000009:adverse effects / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D014456:Ulcer / Q000139:chemically induced
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D014227:Triazines; D051546:Cyclooxygenase 2
keywords: Anti-inflammatory activity; COX-2 inhibitors; Enaminone; HMBC; Histopathology; S-Triazines