2. Academic Validation
  3. (E)-1,3-diphenyl-1H-pyrazole derivatives containing O-benzyl oxime moiety as potential immunosuppressive agents: Design, synthesis, molecular docking and biological evaluation

(E)-1,3-diphenyl-1H-pyrazole derivatives containing O-benzyl oxime moiety as potential immunosuppressive agents: Design, synthesis, molecular docking and biological evaluation

  • Eur J Med Chem. 2016 Jan 27:108:586-593. doi: 10.1016/j.ejmech.2015.12.020.
Xian-Hai Lv 1,  Qing-Shan Li 2,  Zi-Li Ren 1,  Ming-Jie Chu 1,  Jian Sun 3,  Xin Zhang 3,  Man Xing 3,  Hai-Liang Zhu 3,  Hai-Qun Cao 4
Affiliations

Affiliations

  • 1 College of Plant Protection, Anhui Agricultural University, Hefei 230036, PR China.
  • 2 School of Medical Engineering, Hefei University of Technology, Hefei 230009, PR China.
  • 3 State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
  • 4 College of Plant Protection, Anhui Agricultural University, Hefei 230036, PR China. Electronic address: [email protected].
PMID: 26720154 DOI: 10.1016/j.ejmech.2015.12.020
Abstract

A series of novel (E)-1,3-diphenyl-1H-pyrazole derivatives containing O-benzyl oxime moiety were firstly synthesized and their immunosuppressive activities were evaluated. Among all the compounds, 4n exhibited the most potent inhibitory activity (IC50 = 1.18 μM for lymph node cells and IC50 = 0.28 μM for PI3Kγ), which was comparable to that of positive control. Moreover, selected compounds were tested for their inhibitory activities against IL-6 released in ConA-simulated mouse lymph node cells, 4n exhibited the most potent inhibitory ability. Furthermore, in order to study the preliminary mechanism of the compounds with potent inhibitory activity, the RT-PCR experiment was performed to assay the effect of selected compounds on mRNA expression of IL-6. Among them, compound 4n strongly inhibited the expression of IL-6 mRNA.

Keywords

Immunosuppressant; Molecular docking; Oxime ethers; PI3Kγ; Pyrazole.

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