title: (E)-1,3-diphenyl-1H-pyrazole derivatives containing O-benzyl oxime moiety as potential immunosuppressive agents: Design, synthesis, molecular docking and biological evaluation.
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.
authors.affiliation: College of Plant Protection, Anhui Agricultural University, Hefei 230036, PR China.
authors.forename: Xian-Hai
authors.initials: XH
authors.lastname: Lv
authors.affiliation: School of Medical Engineering, Hefei University of Technology, Hefei 230009, PR China.
authors.forename: Qing-Shan
authors.initials: QS
authors.lastname: Li
authors.affiliation: College of Plant Protection, Anhui Agricultural University, Hefei 230036, PR China.
authors.forename: Zi-Li
authors.initials: ZL
authors.lastname: Ren
authors.affiliation: College of Plant Protection, Anhui Agricultural University, Hefei 230036, PR China.
authors.forename: Ming-Jie
authors.initials: MJ
authors.lastname: Chu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
authors.forename: Man
authors.initials: M
authors.lastname: Xing
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
authors.affiliation: College of Plant Protection, Anhui Agricultural University, Hefei 230036, PR China. Electronic address: haiquncao@163.com.
authors.forename: Hai-Qun
authors.initials: HQ
authors.lastname: Cao
mesh_terms: D000818:Animals; D058544:Class Ib Phosphatidylinositol 3-Kinase / Q000378:metabolism; D015195:Drug Design; D005786:Gene Expression Regulation / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010091:Oximes / Q000737:chemistry / Q000494:pharmacology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C000611546:(E)-1,3-diphenyl-1H-pyrazole; D007166:Immunosuppressive Agents; D015850:Interleukin-6; D010091:Oximes; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D012333:RNA, Messenger; D058544:Class Ib Phosphatidylinositol 3-Kinase; C546764:Pik3cg protein, mouse
keywords: Immunosuppressant; Molecular docking; Oxime ethers; PI3Kγ; Pyrazole