Cycloxygenase-2 (COX-2) - A potential target for screening of small molecules as radiation countermeasure agents: An In Silico study

Jayadev Joshi, Tapan K. Barik, Nitisha Shrivastava, Manali Dimri, Subhajit Ghosh, Rahul S. Mandal, Srinivasan Ramachandran, Indracanti P. Kumar

Research output: Contribution to journalArticle

Abstract

Cycloxygenase-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 anti-inflammatory 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.

Original languageEnglish (US)
Pages (from-to)35-45
Number of pages11
JournalCurrent Computer-Aided Drug Design
Volume9
Issue number1
StatePublished - May 3 2013

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Radiation Protection
Computer Simulation
Anti-Inflammatory Agents
Radiation
Inflammation
Bystander Effect
Pharmacopoeias
Libraries
Pharmaceutical Preparations
Neoplasms

Keywords

  • Cycloxygenase-2
  • Radiation protection
  • Screening
  • Small molecules

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Cycloxygenase-2 (COX-2) - A potential target for screening of small molecules as radiation countermeasure agents : An In Silico study. / Joshi, Jayadev; Barik, Tapan K.; Shrivastava, Nitisha; Dimri, Manali; Ghosh, Subhajit; Mandal, Rahul S.; Ramachandran, Srinivasan; Kumar, Indracanti P.

In: Current Computer-Aided Drug Design, Vol. 9, No. 1, 03.05.2013, p. 35-45.

Research output: Contribution to journalArticle

Joshi, J, Barik, TK, Shrivastava, N, Dimri, M, Ghosh, S, Mandal, RS, Ramachandran, S & Kumar, IP 2013, 'Cycloxygenase-2 (COX-2) - A potential target for screening of small molecules as radiation countermeasure agents: An In Silico study', Current Computer-Aided Drug Design, vol. 9, no. 1, pp. 35-45.
Joshi, Jayadev ; Barik, Tapan K. ; Shrivastava, Nitisha ; Dimri, Manali ; Ghosh, Subhajit ; Mandal, Rahul S. ; Ramachandran, Srinivasan ; Kumar, Indracanti P. / Cycloxygenase-2 (COX-2) - A potential target for screening of small molecules as radiation countermeasure agents : An In Silico study. In: Current Computer-Aided Drug Design. 2013 ; Vol. 9, No. 1. pp. 35-45.
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