Structure-based virtual screening and characterization of a novel IL-6 antagonistic compound from synthetic compound database

نویسندگان

  • Jing Wang
  • Chunxia Qiao
  • He Xiao
  • Zhou Lin
  • Yan Li
  • Jiyan Zhang
  • Beifen Shen
  • Tinghuan Fu
  • Jiannan Feng
چکیده

According to the three-dimensional (3D) complex structure of (hIL-6⋅hIL-6R⋅gp 130)2 and the binding orientation of hIL-6, three compounds with high affinity to hIL-6R and bioactivity to block hIL-6 in vitro were screened theoretically from the chemical databases, including 3D-Available Chemicals Directory (ACD) and MDL Drug Data Report (MDDR), by means of the computer-guided virtual screening method. Using distance geometry, molecular modeling and molecular dynamics trajectory analysis methods, the binding mode and binding energy of the three compounds were evaluated theoretically. Enzyme-linked immunosorbent assay analysis demonstrated that all the three compounds could block IL-6 binding to IL-6R specifically. However, only compound 1 could effectively antagonize the function of hIL-6 and inhibit the proliferation of XG-7 cells in a dose-dependent manner, whereas it showed no cytotoxicity to SP2/0 or L929 cells. These data demonstrated that the compound 1 could be a promising candidate of hIL-6 antagonist.

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عنوان ژورنال:

دوره 10  شماره 

صفحات  -

تاریخ انتشار 2016