Identification of novel Interleukin-2 inhibitors through computational approaches

Sobia Ahsan Halim, Omer Mohamed Abdalla, Osman Mesaik Mohammed Ahmed Hassan, Abdul Wadood, Zaheer Ul-Haq, Maria Kontoyianni

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Interleukin-2 (IL-2), is a 15.5-kDa cytokine that is now emerging as a target in drug discovery for novel therapeutic approaches in several autoimmune disorders. In an attempt to identify new inhibitors for the IL-2/IL-2R interaction, virtual screening (VS) was performed. Four different docking programs (GOLD, FlexX, Glide, and LigandFit) in combination with several scoring functions were used to identify novel IL-2/IL-2R interaction inhibitors. VS of a database of 6,000 compounds resulted in the identification of three novel and moderately active hits with IC 50 values ranging from 6.6 to 44.3 μ M. Furthermore, the effect of these three compounds on the expression of IL-2R α was assessed. The three active hits showed dose-dependent inhibitory effects on the expression of IL-2R α with an IC 50 range of 5.8 to 140 μ M. The cytotoxicity of these active hits was assessed using three normal cell-lines: bovine kidney cell-line (MDBK), mouse fibroblast cell-line (3T3), and rat hepatocytes cell-line (CC-1). The compounds were found to have negligible cytotoxicity compared to their IC 50 as IL-2/IL-2R interaction inhibitors. These results demonstrate that our VS protocol can identify novel inhibitors for IL-2/IL-2R interaction that effectively suppress IL-2 production, as well as the expression of IL-2R α. Optimization of these molecules could lead to improved and effective anti-inflammatory therapeutics.

Original languageEnglish
Pages (from-to)345-355
Number of pages11
JournalMolecular Diversity
Volume17
Issue number2
DOIs
Publication statusPublished - May 2013
Externally publishedYes

Fingerprint

interleukins
inhibitors
Interleukin-2
Screening
Cytotoxicity
cultured cells
Cell Line
screening
Fibroblasts
Rats
Drug Discovery
Cells
interactions
Hepatocytes
Molecules
Anti-Inflammatory Agents
scoring
fibroblasts
kidneys
Databases

Keywords

  • FlexX
  • Glide
  • GOLD
  • Interleukin-2
  • LigandFit
  • Virtual screening

ASJC Scopus subject areas

  • Molecular Biology
  • Drug Discovery
  • Information Systems
  • Physical and Theoretical Chemistry
  • Inorganic Chemistry
  • Catalysis
  • Organic Chemistry

Cite this

Halim, S. A., Abdalla, O. M., Mohammed Ahmed Hassan, O. M., Wadood, A., Ul-Haq, Z., & Kontoyianni, M. (2013). Identification of novel Interleukin-2 inhibitors through computational approaches. Molecular Diversity, 17(2), 345-355. https://doi.org/10.1007/s11030-013-9431-4

Identification of novel Interleukin-2 inhibitors through computational approaches. / Halim, Sobia Ahsan; Abdalla, Omer Mohamed; Mohammed Ahmed Hassan, Osman Mesaik; Wadood, Abdul; Ul-Haq, Zaheer; Kontoyianni, Maria.

In: Molecular Diversity, Vol. 17, No. 2, 05.2013, p. 345-355.

Research output: Contribution to journalArticle

Halim, SA, Abdalla, OM, Mohammed Ahmed Hassan, OM, Wadood, A, Ul-Haq, Z & Kontoyianni, M 2013, 'Identification of novel Interleukin-2 inhibitors through computational approaches', Molecular Diversity, vol. 17, no. 2, pp. 345-355. https://doi.org/10.1007/s11030-013-9431-4
Halim SA, Abdalla OM, Mohammed Ahmed Hassan OM, Wadood A, Ul-Haq Z, Kontoyianni M. Identification of novel Interleukin-2 inhibitors through computational approaches. Molecular Diversity. 2013 May;17(2):345-355. https://doi.org/10.1007/s11030-013-9431-4
Halim, Sobia Ahsan ; Abdalla, Omer Mohamed ; Mohammed Ahmed Hassan, Osman Mesaik ; Wadood, Abdul ; Ul-Haq, Zaheer ; Kontoyianni, Maria. / Identification of novel Interleukin-2 inhibitors through computational approaches. In: Molecular Diversity. 2013 ; Vol. 17, No. 2. pp. 345-355.
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