title: Synthesis and characterization of novel oxazines and demonstration that they specifically target cyclooxygenase 2.
abstract: In the present study, we used solution combustion synthesis-bismuth oxide (Bi2O3) as catalyst for the simple and efficient synthesis of 1,2-oxazine based derivatives of 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazoles, 1-arylpiperazine and carbazoles. (4aR,8aR)-4-(4-Methoxyphenyl)-3-((4-(4-methoxyphenyl)piperazin-1-yl)methyl)-4a,5,6,7,8,8a-hexahydro-4H-benzo[e][1,2]oxazine was found to be the most potent compound with a high degree of selectivity in inhibition towards COX2 (1.7 μM) over COX1 (40.4 μM) demonstrating the significance of 1,2-oxazine derivatives in developing COX2 specific inhibitors. Molecular docking analyses demonstrated that an isoleucine residue in the active site of COX1 is responsible for lower affinity to COX1 and increased potency towards COX2. Overall, our study reveals that the new 1,2-oxazine-based small molecules qualify as lead structures in developing COX2-specific inhibitors for anti-inflammatory therapy.
authors.affiliation: Laboratory of Chemical Biology, Department of Chemistry, Bangalore University, Central College Campus, Palace Road, Bangalore 560001, India.
authors.forename: V
authors.initials: V
authors.lastname: Srinivas
authors.affiliation: Department of Studies in Chemistry, Manasagangotri, University of Mysore, Mysore 570006, India.
authors.forename: Chakrabhavi Dhananjaya
authors.initials: CD
authors.lastname: Mohan
authors.affiliation: Laboratory of Chemical Biology, Department of Chemistry, Bangalore University, Central College Campus, Palace Road, Bangalore 560001, India.
authors.forename: C P
authors.initials: CP
authors.lastname: Baburajeev
authors.affiliation: Frontier Research Center for Post-genome Science and Technology, Hokkaido University, Sapporo 060-0808, Japan.
authors.forename: Shobith
authors.initials: S
authors.lastname: Rangappa
authors.affiliation: Department of Studies in Chemistry, Manasagangotri, University of Mysore, Mysore 570006, India.
authors.forename: Swamy
authors.initials: S
authors.lastname: Jagadish
authors.affiliation: Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW Cambridge, United Kingdom.
authors.forename: Julian E
authors.initials: JE
authors.lastname: Fuchs
authors.affiliation: N.D. Zelinsky Institute of Organic Chemistry, Leninsky Prospect, 47, Moscow 119991, Russia.
authors.forename: Alexey Yu
authors.initials: AY
authors.lastname: Sukhorukov
authors.affiliation: Department of Studies in Physics, Manasagangotri, University of Mysore, Mysore 570006, India.
authors.lastname: Chandra
authors.affiliation: Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW Cambridge, United Kingdom.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Mason
authors.affiliation: Department of Studies in Chemistry, Manasagangotri, University of Mysore, Mysore 570006, India.
authors.forename: Kothanahally Shivaramu
authors.initials: KS
authors.lastname: Sharath Kumar
authors.affiliation: Department of Studies in Physics, Manasagangotri, University of Mysore, Mysore 570006, India.
authors.forename: Mahendra
authors.initials: M
authors.lastname: Madegowda
authors.affiliation: Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW Cambridge, United Kingdom.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bender
authors.affiliation: Laboratory of Chemical Biology, Department of Chemistry, Bangalore University, Central College Campus, Palace Road, Bangalore 560001, India.
authors.lastname: Basappa
authors.affiliation: Department of Studies in Chemistry, Manasagangotri, University of Mysore, Mysore 570006, India.
authors.forename: Kanchugarakoppal Subbegowda
authors.initials: KS
authors.lastname: Rangappa
mesh_terms: D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000276:immunology*; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology; D062105:Molecular Docking Simulation; D010078:Oxazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D010078:Oxazines; D051546:Cyclooxygenase 2
keywords: COX2; Oxazines; Proinflammatory disease; SCS-Bi(2)O(3)