title: Structure-based design, synthesis, molecular docking study and biological evaluation of 1,2,4-triazine derivatives acting as COX/15-LOX inhibitors with anti-oxidant activities.
abstract: A set of 1,2,4-triazine derivatives were designed as cyclooxygenase-2 (COX-2) inhibitors. These compounds were synthesized and screened for inhibition of cyclooxygenases (COX-1 and COX-2) based on a cellular assay using human whole blood (HWB) and lipoxygenase (LOX-15) that are key enzymes in inﬂammation. The results showed that 3-(2-(benzo[d][1,3]dioxol-5-ylmethylene)hydrazinyl)-5,6-bis(4-methoxyphenyl)-1,2,4-triazine (G11) was identified as the most potent COX-2 inhibitor (78%) relative to COX-1 (50%). Ferric reducing anti-oxidant power (FRAP) assay revealed that compound G10 possesses the highest anti-oxidant activity. The compound G3 with IC50 value of 124 μM was the most potent compound in LOX inhibitory assay. Molecular docking was performed and a good agreement was observed between computational and experimental results.
authors.affiliation: a Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences .|b Department of Medicinal Chemistry , Faculty of Pharmacy, Shiraz University of Medical Sciences , Shiraz , Iran .
authors.forename: Mehdi
authors.initials: M
authors.lastname: Khoshneviszadeh
authors.affiliation: b Department of Medicinal Chemistry , Faculty of Pharmacy, Shiraz University of Medical Sciences , Shiraz , Iran .
authors.forename: Omolbanin
authors.initials: O
authors.lastname: Shahraki
authors.affiliation: a Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences .
authors.forename: Mahsima
authors.initials: M
authors.lastname: Khoshneviszadeh
authors.affiliation: c Drug Design and Development Research Center, Tehran University of Medical Sciences , Tehran , Iran .
authors.forename: Alireza
authors.initials: A
authors.lastname: Foroumadi
authors.affiliation: a Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences .
authors.forename: Omidreza
authors.initials: O
authors.lastname: Firuzi
authors.affiliation: a Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences .
authors.forename: Najmeh
authors.initials: N
authors.lastname: Edraki
authors.affiliation: d Department of Medicinal Chemistry , Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences , Yazd , Iran , and.
authors.forename: Hamid
authors.initials: H
authors.lastname: Nadri
authors.affiliation: d Department of Medicinal Chemistry , Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences , Yazd , Iran , and.
authors.forename: Alireza
authors.initials: A
authors.lastname: Moradi
authors.affiliation: e Department of Medicinal Chemistry , Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Abbas
authors.initials: A
authors.lastname: Shafiee
authors.affiliation: a Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences .
authors.forename: Ramin
authors.initials: R
authors.lastname: Miri
mesh_terms: D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013058:Mass Spectrometry; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D066244:Proton Magnetic Resonance Spectroscopy; D013055:Spectrophotometry, Infrared; D014227:Triazines / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D052246:Cyclooxygenase 2 Inhibitors; D016859:Lipoxygenase Inhibitors; D014227:Triazines; C093444:1,2,4-triazine
keywords: 1,2,4-triazine; 15-lipoxygenase; Cyclooxygenase; FRAP assay; molecular modeling