title: Cycloxygenase-2 (COX-2)--a potential target for screening of small molecules as radiation countermeasure agents: an in silico study.
abstract: Cyclooxygenase-2 (COX-2) is well established for its role in inflammation, cancer and has also been reported to play a significant role in radiation induced inflammation and bystander effect. It has already been reported to have a role in protection against radiation induced damage, suggesting it to be an important target for identifying novel radiation countermeasure agents. Present study aims at identifying novel small molecules from pharmacopeia using COX-2 as target in silico. Systematic search of the molecules that are reported to exhibit radiation protection revealed that around 30% (40 in 130) of them have a role in inflammation and a small percentage of these molecules (20%; 8 in 40) are reported to act as non-steroidal anti-inflammatory drugs (NSAIDS). Docking studies further clarified that antiinflammatory compounds exhibited higher binding energy (BE). Out of 15 top hits, 14 molecules are reported to have anti-inflammatory property, suggesting the significant role of COX-2 in radiation protection. Further, Johns Hopkins Clinical Compound Library (JHCCL), a collection of small molecule clinical compounds, was screened virtually for COX-2 inhibition by docking approach. Docking of around 1400 small molecules against COX-2, leads to identification of a number of previously unreported molecules, which are likely to act as radioprotectors.
authors.affiliation: Radiation Biosciences Division, Institute of Nuclear Medicine and Allied Sciences, Brig SK Majumdar Road, Timarpur, Delhi, India.
authors.forename: Jayadev
authors.initials: J
authors.lastname: Joshi
authors.forename: Tapan K
authors.initials: TK
authors.lastname: Barik
authors.forename: Nitisha
authors.initials: N
authors.lastname: Shrivastava
authors.forename: Manali
authors.initials: M
authors.lastname: Dimri
authors.forename: Subhajit
authors.initials: S
authors.lastname: Ghosh
authors.forename: Rahul S
authors.initials: RS
authors.lastname: Mandal
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Ramachandran
authors.forename: Indracanti P
authors.initials: IP
authors.lastname: Kumar
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology; D003198:Computer Simulation; D017076:Computer-Aided Design; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D062105:Molecular Docking Simulation; D011837:Radiation-Protective Agents / Q000737:chemistry* / Q000494:pharmacology*; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D011837:Radiation-Protective Agents; D054852:Small Molecule Libraries; D051546:Cyclooxygenase 2