Identification of nitroimidazole-oxime derivatives targeting the polo-box domain of polo-like kinase 1
- Bioorg Med Chem. 2017 Dec 15;25(24):6581-6588. doi: 10.1016/j.bmc.2017.10.035.
- 1. School of Life Sciences, Shandong University of Technology, Zibo 255049, PR China; Elion Nature Biological Technology Co., Ltd, Nanjing 210046, PR China. Electronic address: [email protected].
- 2. School of Life Sciences, Shandong University of Technology, Zibo 255049, PR China.
- 3. Shandong Experimental High School, Jinan 250001, PR China.
- 4. Elion Nature Biological Technology Co., Ltd, Nanjing 210046, PR China.
Recent progress in the development of small molecular skeleton-derived polo-like kinase (PLK1) catalytic domain (KD) inhibitors has led to the synthesis of multiple ligands with high binding affinity. However, few systematic analyses have been conducted to identify key PLK1-PBD domain and characterize their interactions with potent PLK1 inhibitors. Therefore, we designed a series of PLK1-PBD inhibitors with an in silico scaffold modification strategy. A docking simulation combined with a primary screen in vitro were performed to filter for the lead compound, which was then substituted, synthesized and evaluated by a variety of bioassays. The biological profile of 4v suggests that this compound may be developed as a potential Anticancer agent.