title: Synthesis, biological evaluation, and molecular docking studies of N,1,3-triphenyl-1H-pyrazole-4-carboxamide derivatives as anticancer agents.
abstract: A series of N,1,3-triphenyl-1H-pyrazole-4-carboxamide derivatives have been designed, synthesized and evaluated for their potential antiproliferation activity and Aurora-A kinase inhibitory activity. Among all the compounds, compound 10e possessed the most potent biological activity against HCT116 and MCF-7 cell lines with IC(50) values of 0.39±0.06μM and 0.46±0.04 μM, respectively, which were comparable to the positive control. Compound 10e also exhibited significant Aurora-A kinase inhibitory activity (IC(50)=0.16±0.03 μM). Docking simulation was performed to position compound 10e into the active site of Aurora-A kinase, in order to get the probable binding model for further study. The results of Western-blot assay demonstrated that compound 10e possessed good Aurora-A kinase inhibitory activity against HCT116. Based on the preliminary results, it is deduced that compound 10e with potent Aurora-A kinase inhibitory activity may be a potential anticancer agent.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, PR China.
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.forename: Xiang
authors.initials: X
authors.lastname: Lu
authors.forename: Man
authors.initials: M
authors.lastname: Xing
authors.forename: Xian-Hui
authors.initials: XH
authors.lastname: Yang
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Zhao
authors.forename: Hai-Bin
authors.initials: HB
authors.lastname: Gong
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D064127:Aurora Kinases; D001665:Binding Sites; D045744:Cell Line, Tumor; D003198:Computer Simulation; D045325:HCT116 Cells; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; C574782:N,1,3-triphenyl-1H-pyrazole-4-carboxamide; D011720:Pyrazoles; C031280:pyrazole; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases